Lyme disease can be classified using the terminology of syphilis. In this series of 95 cases from the upper midwest, early cases, defined as an illness of less than 2 months, were more likely to have lived in or recently visited a highly endemic area. Unlike late cases, early cases presented entirely in the nonwinter months (p less than .001). Early disease was further subdivided into primary and secondary disease. Ninety percent of primary and 43% of secondary cases had erythema migrans, while no late cases had active erythema migrans (p less than .001). Clinical manifestations of nonspecific inflammation, except for arthralgia, were more common in early than late disease (p less than .01). In secondary cases, monoarticular arthritis was slightly more common than polyarticular arthritis, with the reverse occurring in late disease (p less than .05). Indirect fluorescent antibody testing revealed a ratio of IgM to IgG antibodies to be helpful in distinguishing early from late disease. Antibacterial therapy in early, primary cases caused Jarisch-Herxheimer reaction 7% of the time. Despite longer and more frequent parenteral therapy, late Lyme disease frequently required retreatment, owing to poor clinical response (p less than .05).