To analyze the diagnoses, serological test results, and treatment results of the patients evaluated in a Lyme disease clinic, both prior to referral and from current evaluation. Retrospective case survey of prescreened patients. Research and diagnostic Lyme disease clinic in a university hospital. All 788 patients referred to the clinic during a 4.5-year period who were thought by the referring physician or the patient to have a diagnosis of Lyme disease. Symptoms and signs of disease, immunodiagnostic tests of Lyme disease, and tests of neurological function. Of the 788 patients, 180 (23%) had active Lyme disease, usually arthritis, encephalopathy, or polyneuropathy. One hundred fifty-six patients (20%) had previous Lyme disease and another current illness, most commonly chronic fatigue syndrome or fibromyalgia; and in 49 patients, these symptoms began soon after objective manifestations of Lyme disease. The remaining 452 patients (57%) did not have Lyme disease. The majority of these patients also had the chronic fatigue syndrome or fibromyalgia; the others usually had rheumatic or neurological diseases. Of the patients who did not have Lyme disease, 45% had had positive serological test results for Lyme disease in other laboratories, but all were seronegative in our laboratory. Prior to referral, 409 of the 788 patients had been treated with antibiotic therapy. In 322 (79%) of these patients, the reason for lack of response was incorrect diagnosis. Only a minority of the patients referred to the clinic met diagnostic criteria for Lyme disease. The most common reason for lack of response to antibiotic therapy was misdiagnosis.