During 1983-1986, 5,016 cases of Lyme disease were reported to the Centers for Disease Control. Cases were acquired in 31 states; however, 86% of the cases were acquired in seven states: Massachusetts, Rhode Island, Connecticut, New York, New Jersey, Wisconsin, and Minnesota. For 63% of patients the disease began in summer; 52% recalled a tick bite. Erythema chronicum migrans (ECM) occurred in 91% of the patients; arthritis, in 57%; neurologic complications, in 18%; and cardiac manifestations, in 10%. When serum samples were obtained greater than or equal to 21 days after onset of symptoms, 14% (6 of 42) with ECM alone and 19% (17 of 89) with complicated Lyme disease (ECM plus organ-system involvement) had positive serologic tests. Antimicrobial therapy did not appear to affect serologic response. Lyme disease is now the most commonly reported tick-borne illness in the United States and has been reported from 32 states since 1980. Physicians nationwide need to be familiar with the protean signs and symptoms associated with Lyme disease and with the limitations of current serologic techniques in diagnosing early illness.