In the United States, since 2001, an average of 265 mumps cases (range: 231-293 cases) have been reported each year, and in Iowa, an average of five cases have been reported annually since 1996. However, in 2006, by March 28, a total of 219 mumps cases had been reported in Iowa, and an additional 14 persons with clinically compatible symptoms were being investigated in three neighboring states (11 in Illinois, two in Nebraska, and one in Minnesota) in what has become the largest epidemic of mumps in the United States since 1988. This report summarizes and characterizes the ongoing mumps epidemic in Iowa, the public health response, and recommendations for preventing further transmission.