The efficacy and safety of a single 1 g oral dose of azithromycin was evaluated in 100 male patients with non-gonococcal urethritis (NGU). Enrolled were men with > or = 5 polymorphonuclear leukocytes (PMNL)/high power field (HPF) (x 1000 magnification) in a Gram-stained smear of urethral discharge with or without symptoms and signs of NGU. Of the 66 evaluable patients, Chlamydia trachomatis was isolated from 18 cases (27.3%) and Ureaplasma urealyticum from 12 cases (18.2%). After treatment, signs and symptoms disappeared from 59 cases (89.4%). Forty-four cases (66.7%) showed reduced PMNL/HPF. C. trachomatis was eradicated in 18 cases (100%) and U. urealyticum in 12 cases (83.3%). One patient complained of mild dizziness, moderate nausea, and palpitations. Single 1 g oral dose of azithromycin appears to be effective and safe for treating chlamydial, non-chlamydial, and ureaplasmal NGU. In addition, its ease of use encourages patient compliance.