Adult patients with typical solitary erythema migrans, participating in prospective therapeutic studies on early Lyme borreliosis at the Lyme borreliosis Outpatient's Clinic, University Department of Infectious Diseases in Ljubljana, in 1991 to 1993, and followed up for 1 year, were included in the study. Only patients who were treated with azithromycin or doxycycline and in whom Borrelia burgdorferi was isolated from the border of the skin lesion prior to institution of antibiotic treatment were selected for presentation in this report. Fifty-eight patients received azithromycin (500 mg twice daily for the first day, followed by 500 mg once daily for 4 days) and 42 patients received doxycycline (100 mg twice daily for 14 days). The median duration of skin lesions after the beginning of treatment was 6.5 (2-30) days in the azithromycin group and 8 (2-35) days in the doxycycline group (non-significant difference). During the follow-up of 12 months one patient in each group developed major later manifestations of Lyme borreliosis and in 19 patients minor manifestations appeared: in nine (15.5%) treated with azithromycin and in ten (23.8%) receiving doxycycline. In one patient in the azithromycin group and in one patient in the doxycycline group B. burgdorferi was isolated from normal appearing skin at the site of previous erythema migrans 2 months after the institution of antibiotic therapy. Five (8.6%) patients receiving azithromycin and nine (21.4%) patients receiving doxycycline reported mild to moderate gastrointestinal discomfort. In addition, five patients treated with doxycycline developed photosensitivity.