The lack of practical methods for a laboratory diagnosis of influenza C virus infections and the seemingly benign nature of the virus contribute to the fact that 50 years after its first isolation, relatively little is known about the epidemiology and the clinical impact of this virus. Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify influenza C RNA fragments from clinical specimens. Two hundred otherwise healthy adults with recent onset of a common cold were studied. Nasopharyngeal aspirates were collected at entry to the study and 1 week later. Serum samples for antibody determinations were obtained at the first visit and after 3 weeks. Influenza C was detected in 7 of the 200 patients by 2 different RT-PCR formats. All 7 patients had a significant increase in antibody titers between serum samples collected during the acute and convalescent phases of the illness. Influenza C appears to be one of the many viruses that cause acute upper respiratory tract infections in adults.