This study was undertaken to characterize the epidemiology and clinical presentation of infection with Chlamydia pneumoniae in a population composed primarily of middle-aged and older adults. Pharyngeal swabs and acute and convalescent phase sera were obtained from outpatients presenting with signs and symptoms of an acute respiratory infection. Sera were examined using the micro-immunofluorescence (MIF) test to detect antibody to Chlamydia pneumoniae and complement fixation tests to detect Mycoplasma pneumoniae, influenza A virus, influenza B virus, respiratory syncytial virus and adenovirus. Pharyngeal swab specimens were cultured for Chlamydia pneumoniae and tested for Chlamydia pneumoniae by the polymerase chain reaction (PCR). A total of 743 patients with a mean age of 40.5 +/- 16.1 years were enrolled in the study. Twenty-one patients were serologically positive for acute Chlamydia pneumoniae infection in the MIF test. PCR was positive in 15 of the 20 serologically positive patients tested. Acute Chlamydia pneumoniae infection was identified in 3% (2/76) of subjects with pneumonia, 5% (12/247) of those with bronchitis, 5% (3/61) of those with sinusitis only and 2% (2/103) of those with pharyngitis only. Of the 21 patients with Chlamydia pneumoniae infection, seven (mean age of 33 years) had an antibody pattern suggesting a primary infection while 14 (mean age of 54 years) had a reinfection pattern. Patients with reinfection had milder disease than those with primary infection. PCR testing in the current study confirms the previously proposed serologic criteria of acute Chlamydia pneumoniae infection.