Clinical and serologic data were collected on 667 University of Washington students who presented to the David Hall Student Health Center between 1983 and 1987 with acute respiratory disease. Sera were tested for evidence of acute or past infections with Chlamydia pneumoniae strain TWAR, Chlamydia trachomatis, Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenovirus, and respiratory syncytial virus. Pharyngeal swab specimens were cultured for C. pneumoniae and C. trachomatis, but not for the other agents. Evidence of acute infection with C. pneumoniae was found in 20 patients and evidence of an acute infection with M. pneumoniae in 29 patients. C. pneumoniae was associated with 9% and M. pneumoniae with 11% of 149 pneumonias diagnosed clinically, and with 20% and 22%, respectively, of the 59 pneumonias confirmed on chest radiograph. There was no evidence of seasonality in C. pneumoniae or M. pneumoniae infections. Compared with patients with M. pneumoniae, patients with C. pneumoniae were less likely to have a temperature greater than 37.8 degrees C (10% vs. 34%), but were more likely to present with a sore throat (80% vs. 52%) or hoarseness (30% vs. 3%). The mean number of days from onset of symptoms until enrollment was longer in patients with C. pneumoniae infections than in those with M. pneumoniae (12.8 vs. 7.9 days), or those with a viral infection (12.8 vs. 7.3 days), suggesting a more gradual onset of disease caused by C. pneumoniae.