A prospective study was conducted over a 3-month winter period in three general practice clinics in an urban population in southern Israel to identify the etiological agents of respiratory tract infections (RTI) in adults. RTI was defined as an acute febrile illness with cough, coryza, sore throat or hoarseness. Serum samples were taken from all patients in both the acute and convalescent phases of their illness. Tests were conducted for detection of 17 microorganisms known to cause RTI, including serological tests for 16 known pathogens. An etiological diagnosis was established in 80 (66%) of the 122 patients who participated in the study. The distribution of the etiological agents was as follows: influenza B virus in 27 (22%) patients. Chlamydia pneumoniae in 22 (18%), Legionella spp. in 15 (12%), Mycoplasma pneumoniae in 13 (11%), influenza A virus in 11 (9%), Bordetella pertussis in 9 (7%), adenovirus in 4, Epstein Barr virus in 4, Haemophilus influenzae in 3, beta-hemolytic streptococci in 3, Streptococcus pneumoniae in 2, respiratory syncytial virus in 2, parainfluenza 1 virus in 2 and parainfluenza 2 virus in 1. No patients were found to be infected with Coxiella burnetii, Moraxella catarrhalis or parainfluenza 3 virus. More than one pathogen was identified in 27 (34%) patients in whom an etiological diagnosis was established. It is concluded that RTI is caused by a broad spectrum of etiological agents, a considerable number of patients having evidence of infection with more than one pathogen. The therapeutic significance of these findings should be elucidated in further studies.