The effect of minocycline on nongonococcal urethritis (NGU) was investigated, with particular reference to its action against Chlamydia trachomatis. Preliminary laboratory studies showed that the drug was active against a laboratory chlamydial strain (Lb4f) in vitro. A group of 133 men with first attacks of NGU was then treated with minocycline, 100 mg twice daily for 3 weeks. Isolates of C trachomatis were obtained from 33 of these men before treatment; all of them gave negative results on cell culture after therapy. Of the 133 patients, 119 (90%) had symptoms on their first attendance, but after one week's treatment only 16 of the 133 (12%) and after 3 weeks 6 of the 133 (5%) had symptoms. All 133 men had demonstrable urethritis initially; by the end of the first week of treatment only 43 of the 133 (32%) and by the end of the third week 32 of the 133 (24%) had evidence of urethritis. There were no differences in clinical response between the Chlamydia-positive and Chlamydia-negative groups. A group of 24 female sexual contacts of men with NGU yielded C trachomatis on cell culture. After 3 weeks' therapy with minocycline all these women gave negative results on cell culture. It is concluded that minocycline is a useful addition to existing remedies for NGU. The future structure of treatment trials for NGU is discussed.