"These people may have exposed other people on those planes or in these airports," said Kevin Teale, a spokesman for the Iowa Department of Public Health.
The mumps epidemic is the nation's first in 20 years.
Iowa usually gets just five cases of mumps a year.
"This year so far we're well over 500 and there's no signs that it's going to slow down soon," Teale told CBS Radio News.
The disease also has been seen in six neighboring states, according to the U.S. Centers for Disease Control and Prevention. As of Monday, Nebraska has 43 reported cases; Kansas, 33; Illinois, four; Missouri, four; Wisconsin, four; and Minnesota, one.
Teale said this is the same strain of mumps that hit Britain two years ago.
The Iowa health department identified two people who were potentially infectious when they were traveling in late March and early April.
Officials in other states have not yet linked any cases to the air travelers. But because the illness's incubation is two to three weeks, cases may not begin appearing until about now, Teale said.
"Fortunately, for most people, mumps is a fairly mild illness and they get over it quickly," Teale said. "Some people may have it without even any symptoms and not even be aware that they're spreading it."
This week the CDC put out an advisory about the passengers to state health departments. "Infectious diseases can travel easily on planes and other modes of transportation," said Dr. Jane Seward, acting deputy director of the CDC's viral diseases division.
The first traveler is executive director of a Waterloo, Iowa, downtown development organization who in late March was in a delegation that traveled to Washington, D.C.
The woman, Terry Poe Buschkamp, had earlier visited the Dominican Republic where she thinks she may have caught the bug. Health officials did not release her name, but she has acknowledged her infection to the media.
Buschkamp, 51, left Waterloo, Iowa, on March 26 on a Mesaba Airlines flight to Minneapolis and then flew Northwest Airlines to Detroit. On March 26, she flew to Washington, D.C.'s Reagan National Airport. During her visit, she shook hands with Iowa's two U.S. senators, Tom Harkin and Charles Grassley, she said.
She returned to Waterloo on March 29 on Northwest and Mesaba flights, with a stop in Minneapolis.
She said she developed a scratchy throat upon her return, and after hearing reports of a mumps outbreak, went to a doctor for testing. She got confirming test results six days later.
During those six days, she had been to church and numerous work events, including an April 1 pub crawl that involved about 370 people. Mumps has been a mild disease for most people, but Buschkamp found the length of time she was able to spread the virus before learning her test results alarming.
"That's the real story," she said.
She said two of her fellow travelers have told her they have mumps-like symptoms, but have declined to see a doctor about it.
The second person was a young man returning from vacation in Arizona on April 1, Teale said.
He flew American Airlines, from Tucson to Dallas, then to Fayetteville, Ark., to St. Louis and finally to Cedar Rapids, Iowa.
Two people — and nine flights? "It's hard to get anywhere (from Iowa) without connecting," Teale explained.
Mumps is a virus-caused illness spread by coughing and sneezing. The most common symptoms are fever, headache and swollen salivary glands under the jaw. But it can lead to more severe problems, such as hearing loss, meningitis and fertility-diminishing swollen testicles.
No deaths have been reported from the current epidemic.
A two-dose mumps vaccine is recommended for all children, and is considered highly — but not completely — effective against the illness. About a quarter of the Iowans who have suspected cases got the vaccine, Teale said.