The itchy passenger was Lise Sievers of Red Wing, Minn., a 50-year-old woman returning home from Uganda, where she was working to adopt two children. Sievers noticed the rash and told her mother, who got worried and called health officials in Indiana.
"It's just a case of bed bugs," Sievers told ABC News affiliate WLS after exiting the plane. "I think I'm going to empty a jar of bed bugs on my mom's bed tonight."
Other passengers aboard Flight 3163 feared the worst as officers wearing Hazmat suits studied the rash, sending photos to U.S. Centers for Disease Control and Prevention headquarters in Atlanta.
"They didn't tell us very much at all," one passenger told WLS, describing a scene that could have come from the movie "Contagion." "When they come on in masks and gloves, you think the worst."
Monkeypox is a rare and sometimes fatal disease similar to smallpox that occurs mostly in central and western Africa. It's contracted through contact with infected animals or their bodily fluids, and can spread among humans through fluids and contaminated clothes or bedding, according to the CDC.
The monkeypox rash consists of raised, fluid-filled bumps, and is usually accompanied by fever, headache and lymph node swelling. Bed bug bites, on the other hand, cause a swollen and red area that may or may not be itchy, without the other symptoms.
Sievers, who was sitting near the bathroom on the plane, recalled the worried looks from other passengers when it became clear she was the cause of the quarantine.
"You could see them thinking, 'Is it safe to use the bathroom?'" she told WLS.
After studying the rash and searching for other signs of infectious disease, health officials released Sievers and her fellow passengers.
"Medical staff at CDC and the Chicago Department of Public Health reviewed the case and, based on the patient's symptoms and photographs of the rash, it does not appear that the signs and symptoms are consistent with a monkeypox infection," the CDC said in a statement. "The ill passenger was advised to seek medical care and the rest of the passengers were released from the plane."
Dr. Donald Henderson, a professor of medicine and public health at the University of Pittsburgh and former director of the Office of Public Health Emergency Preparedness, said the quarantine was an unusual and unhelpful move.
"In the exceptional circumstance in which a passenger with a serious transmissible disease is discovered on a plane, the best course of action would be to explain to the passengers what the disease might be and to give them instructions to contact their physicians and to call a designated CDC emergency number should they develop any one of a number of symptoms," he said. "The worst thing that can be done is to spread alarm and concern, delay air travel, and publicly exercise an array of unnecessary emergency measures."
Dr. Martin Cetron, director of quarantine for the CDC, said health officials board planes to investigate possible infectious diseases upward of 40 times a month. The flights are usually delayed only a few minutes, and passengers might not even be aware of it. But two or three times a year there is a significant delay, like the one at Chicago Midway, he said.
After two agonizing hours on the tarmac, passengers were happy to learn that the rash was not the result of something more serious.
"Of course, you're relieved when they say it is just a case of bug bites," passenger Kayla Sanders told WLS.
Undeterred, Sievers plans to return to Uganda in a month to finalize the adoption of the two children.
ABC News affiliate WLS in Chicago contributed to this story.