Azithromycin is a novel azalide macrolide active against Chlamydia trachomatis and Ureaplasma urealyticum. High persistent tissue concentrations allow short courses or even single doses to be considered. Sixty-two patients were studied, 19 received azithromycin 1 g in a single dose, 22 received azithromycin 500 mg in a single dose on day 1 followed by 250 mg once daily for 2 days and 21 received doxycycline 200 mg in a loading dose followed by 100 mg every 12 h for 7 days. Efficacy of these 3 regimens was compared in the treatment of non-gonococcal urethritis (NGU). Clearance of C. trachomatis from post-treatment cultures was satisfactory with all regimens. Response defined as the absence of symptoms and reduction in polymorphonuclear leucocytes in a Gram stained smear of urethral secretion to less than 5 cells per hpf (x 100 objective) was statistically better for the 3 day regimen of azithromycin than for the other 2 regimens. All treatments were well tolerated. Three days or single doses of azithromycin compared to 7 days of tetracycline (or 10-14 days as is often prescribed) have obvious advantages for patient compliance.