The efficacy of oral azithromycin (500 mg daily for 10 days or 500 mg on alternate days for 11 days) in 100 patients with seropositive syphilis was studied. Clinical manifestations regressed more rapidly in azithromycin-treated patients compared with patients who received erythromycin or penicillin, and there was also a more rapid reduction in serum antibody levels. In 90.3% of patients, the complete resolution of classic serological tests was observed within 4 months of completion of the azithromycin treatment. The immobilization (TPI) test and absorbed fluorescent treponema antibody tests became negative 12 months after treatment in 40% of patients. After 4 years of follow-up, no symptoms of neurosyphilis or syphilitic changes of visceral organs were observed.