We studied the prevalence and the clinical and laboratory findings of infectious mononucleosis in ambulatory adult patients with the presenting symptom of sore throat. Extensive clinical data, heterophil antibody test, and differential leukocyte count were obtained prospectively for 709 patients, aged 16 to 73 years, seen in four primary care settings. Heterophil tests were positive in 15 of 709 patients (2%); four of the 15 had greater than 10% atypical lymphocytes. No heterophil-negative patient had greater than 10% atypical lymphocytes. Heterophil-positive patients had mild disease; none was older than 40 years. Of 70 symptoms and signs evaluated, four were found significantly more often (p less than 0.005 for each) in the heterophil-positive patients: palatine petechiae, posterior auricular adenopathy, marked axillary adenopathy, and inguinal adenopathy. If any of these four easily shown physical findings was present, the likelihood of the patient having heterophil antibody was considerably increased; if absent, the probability of infectious mononucleosis was so low that not ordering a heterophil test or differential leukocyte count would have been efficient and safe.