Thirty-two patients with the onset of erythema chronicum migrans, Lyme arthritis, or both in mid-1976 were studied prospectively. The skin lesion (24 patients) typically lasted about 3 weeks, beginning as a red macule or papule that expanded to form a large ring with central clearing. Associated symptoms ranged from none to malaise, fatigue, chills and fever, headache, stiff neck, backache, myalgias, nausea, vomiting, and sore throat. Three patients had been bitten by ticks at the site of the initial lesion 4 to 20 days before its onset. Nineteen patients suddenly developed a monoarticular or oligoarticular arthritis 4 days to 22 weeks (median, 4 weeks) after onset of the skin lesion; eight developed arthritis without a preceding skin lesion. Seven of these 27 experienced migratory joint pains. Arthritis attacks, most commonly in the knee, were typically short (median, 8 days) but sometimes persisted for months. Other manifestations included neurologic abnormalties, myocardial conduction abnormalities, serum cryoprecipitates, elevated serum IgM levels, and elevated erythrocyte sedimentation rates. The diagnostic marker is the skin lesion; without it, geographic clustering is the most important clue.