OBJECTIVES--To evaluate gonococcal (GU) and nongonococcal urethritis (NGU), chlamydia antigen, and serostatus for syphilis and human immunodeficiency virus (HIV) among males attending a Malawian STD clinic with complaints of urethral discharge and/or dysuria. To collect demographic and behavioural data and to determine the effectiveness of five treatments for urethritis. METHODS--Urethritis was diagnosed using microscopy and culture for Neisseria gonorrhoeae. Sera were screened with rapid plasma reagin (RPR) and if reactive, with microhaemagglutination for Treponema pallidum (MHA-TP). HIV antibodies and chlamydia antigen were detected using enzyme immunoassay. Patients were randomised for treatment, cure was assessed 8-10 days later. RESULTS--At enrolment, GU was diagnosed in 415 (80.3%) and NGU in 59 (11.2%) of 517 males. Chlamydia antigen was found in 26 (5.2%) of 497 specimens tested. Syphilis seropositivity rate (RPR and MHA-TP reactive) was 10.7%. Overall HIV seroprevalence was 44.2%; 71.7% of men with reactive syphilis serology were HIV(+) compared with 40.9% of syphilis seronegatives (OR: 3.6, p < 0.001). Trimethoprim 320 mg/sulphamethoxazole 1600 mg by mouth for 2 days (TMPSMX), or the combination of amoxicillin 3 gm, probenicid 1 gm, and clavulanate 125 mg by mouth once (APC), failed to cure gonorrhoea effectively. Amoxicillin 3 gm, probenicid 1 gm, and clavulanate 125 mg, by mouth once with doxycycline 100 mg BID for 7 days (APC-D), gentamicin 240 mg IM once (GENT), ciprofloxacin 250 mg by mouth once (CIPRO) cured 92.9% to 95% of gonorrhoea. APC-D treatment did not generate less NGU at follow-up. HIV serostatus did not affect cure of urethritis. CONCLUSION--All patients presenting with urethritis should be treated syndromically using a simple algorithm and screened for syphilis seroreactivity for appropriate treatment and counselling