BACKGROUND: Although genital herpes has emerged as the most common cause of genital ulcers in Southern Africa, treatment for herpes is not available routinely in the region. This study was performed to determine the etiology of genital ulcers in men in Durban and assess other sexually transmitted infections-related symptoms, presentation, and treatment patterns in this group. METHODS: Polymerase chain reaction (PCR) tests were performed on specimens from consecutive male patients with genital ulcers to detect sexually transmitted pathogens. PCR was also performed for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis on urethral specimens from consecutive subjects with dysuria or urethral discharge. Antibody tests for syphilis and herpes simplex virus type-2 (HSV-2) and human immunodeficiency virus antibodies were performed. RESULTS: Of 162 patients enrolled with genital ulcers, 77.7% were human immunodeficiency virus-positive and 84.6% had antibodies to HSV-2. PCR results showed the following prevalences: HSV-2 53.7%, lymphogranuloma venereum 13.6%, Treponema pallidum 3.7%, Hemophilus ducreyi 1.2%, mixed infections 6.2%, and no pathogens identified 33.3%. One case of donovanosis was diagnosed clinically. In men with HSV-2 ulcers, delay before attendance recorded for 68 men was 1 to 3 days (24%), 4 to 7 days (47%), 8 to 14 days (12%), 15 to 30 days (12%), and >30 days (6%). History-taking using prompting increased the sensitivity but decreased the specificity and positive predictive value of reported genital ulceration when assessed against ulcers seen on examination. CONCLUSIONS: Men at risk of genital ulcers should be asked about relevant symptoms with and without prompting and examined clinically to maximize the likelihood of correct diagnosis and treatment. The finding of a high prevalence of HSV-2 and associated dysuria cautions against providing empirical treatment for gonorrhoea and chlamydia in ulcer patients with dysuria but without urethral discharge. Innovative strategies to limit the burden of HSV-2 infection in this population are required.