The federal investigation is reportedly into possible misuse of campaign funds, but Jackson was also under a House Ethics Committee investigation over dealings with imprisoned ex-Illinois Gov. Rod Blagojevich, but it was unclear how the committee would proceed with the resignation. The committee could still decide to release a final report with their findings, but they no longer have the power to punish him.
Jackson, 47, was never charged with wrongdoing and in his resignation letter wrote, "they are my mistakes and mine alone."
The letter also immediately prompted his attorneys to come forward also though they offered few details of the probe reportedly into misuse of campaign funds.
"Mr. Jackson is cooperating with the investigation. We hope to negotiate a fair resolution of the matter but the process could take several months," said a statement from Jackson attorneys including former U.S. Attorney in Chicago Dan Webb. "During that time, we will have no further comment and urge you to give Mr. Jackson the privacy he needs to heal and handle these issues responsibly."
Experts said confirmation by Jackson of the federal investigation and his resignation signaled more details are likely to follow.
"I think it won't be too long before we hear an announcement of a plea agreement," said Bruce Reinhart, a white-collar defense lawyer in West Palm Beach, Fla., who was a federal prosecutor for 19 years. "The government doesn't like people who are going to plead guilty to abusing public office to remain in a position of public trust. ... Resignation would be a significant bargaining chip for Congressman Jackson in order to get a better deal from the government."
Late Wednesday the longtime Chicago congressman's father, the Rev. Jesse Jackson Sr., told reporters his son resigned because he didn't believe he could continue to serve effectively while also trying to get well.
"He made the decision to choose his health," Jackson said.
He also said there is no way of knowing how long it will take for his son to recover from what he characterized as an "internal unresolved challenge."
"It's not the kind of illness you can put a timetable on," Jackson said, adding that he is confident that his son "will get well in time."
Jackson first took office in 1995 after winning a special election in a largely urban and Democratic district and began his career in Washington with a star power and pedigree that set him apart from his hundreds of other House colleagues.
But despite high expectations, he largely went unnoticed as a policymaker.
Jackson went on medical leave in June, though his office was never forthcoming about details about his condition, his whereabouts or if he would return.
It was later revealed that he was being treated at the Mayo Clinic for bipolar disorder and gastrointestinal issues. He returned to his Washington home in September but went back to the clinic the next month, with his father, the Rev. Jesse Jackson, saying his son had not yet "regained his balance."
Jackson has not detailed what his treatment entails. Attempts by The Associated Press to locate Jackson were unsuccessful, and family members either declined to comment or could not be reached.
In the letter Jackson said that he returned to Washington the first time against the recommendations of his doctor and then needed to return. He said over the months as his health had "deteriorated" his ability to serve his constituents had "diminished."
"My health issues and treatment regimen have been incompatible with service in the House of Representatives," he wrote.
Bipolar disorder used to be known as manic-depression and it can cause severe mood swings that interfere with the ability to handle daily tasks. Prescription drugs including the mood stabilizer lithium and antidepressants can help manage the symptoms, but it often takes time to find the right drug, or combination of drugs, to be effective.
Fellow congressman said that Jackson had difficulty in the decision to resign.
Rep. Bobby Rush, a fellow Chicago Democrat, told reporters that he spoke to a melancholy Jackson on the phone early Wednesday morning — hours before Jackson submitted his resignation letter.
"He sounded very sorrowful — in so much pain . . . that he wouldn't be able to serve in Congress anymore," Rush said.
Voters in the Chicago area district had been largely supportive of Jackson, who has easily won every election since winning a special election in 1995. But as Jackson's medical leave was prolonged and new details released, there were cracks in that support.
Voter Rodney Butler said Jackson had not handled his leave of absence well. The 62-year-old retiree described the congressman's approach as "hush-hush" and said it made Jackson seem like he did something wrong.
The timing of Jackson's leave and the way it was handled invited more scrutiny. Jackson's leave was announced just after a former fundraiser connected to the Blagojevich allegations was arrested on unrelated medical fraud charges.
The vacancy left by Jackson's departure creates a rare opportunity for someone else to represent his district, which is made up of South Side Chicago neighborhoods, several southern suburbs and rural areas.
Even before the resignation the gambit of potential successors floated around Chicago. Prominent Chicago attorney Sam Adam Jr., a onetime attorney for Blagojevich and R&B singer R. Kelly, said he'd be interested. Other names circulating are Chicago Aldermen Sandi Jackson and Anthony Beale, Cook County Board President Toni Preckwinkle and former one-term U.S. Rep. Debbie Halvorson.
Illinois Gov. Pat Quinn, a Democrat, will schedule a re-election in the coming days. He said he planned to set both a primary and a general election.