The activity of tetracycline hydrochloride and minocycline hydrochloride was compared against 12 strains of Chlamydia trachomatis and Ureaplasma urealyticum; minocycline was more active in vitro against both organisms. A group of 145 men with non-gonococcal urethritis was treated for one week with either tetracycline hydrochloride 500 mg six hourly or minocycline 50 mg twice daily. The clinical results obtained were similar: 61 of 77 (79%) men treated with tetracycline and 53 of 68 (78%) men treated with minocycline were free from urethritis one to two weeks after completing treatment. Both antibiotics were clinically effective against C trachomatis, but activity against U urealyticum was less consistent. Side effects were noted in 14 (18%) men treated with tetracycline and eight (12%) men treated with minocycline; they were predominantly gastrointestinal.