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Conflicting data exist regarding whether HIV infection leads to changes in the clinical manifestations and severity of genital ulcer disease (GUD).To determine the impact of HIV on the etiology and clinical severity of GUD.From July 1990 to July 1992, consecutive patients presenting to the two Baltimore City Health Department (BCHD) Sexually Transmitted Diseases clinics were approached as candidates for enrollment in a prospective study to determine factors associated with the transmission and acquisition of sexually transmitted diseases (STDs).Of the 1368 patients who presented to the BCHD, 214 (16%) had genital ulcerations: 160 (21%) of 757 men and 54 (9%) of 611 women. Among the patients with GUD who had undergone HIV testing, 28 (14%) of 204 were infected with HIV: 25 (17%) of 151 men and 3 (6%) of 53 women. Although both groups–those infected with HIV and those not infected with HIV–presented with GUD of similar duration (10 versus 11 days;P = 0.17), multiple lesions were found more frequently in men with HIV infection than in uninfected men: 87% versus 62% (P = 0.02). Although not statistically significant, GUD in men with HIV infection more often were deep (64% versus 44%, respectively) rather than superficial (36% versus 57%, respectively;P = 0.08), and larger (505 mm 2 versus 109 mm 2 ;P = 0.06). Primary syphilis caused more GUD among men with HIV infection than among uninfected men: 9 (36%) of 25 versus 24 (19%) of 126, respectively (P < 0.01). Secondary syphilis was diagnosed with concomitant GUD more frequently among men with HIV infection than among uninfected men: 3 (13%) of 25 versus 3 (2%) of 123, respectively (P < 0.01).In this study, patients who presented with GUD were more likely to be infected with HIV. A higher proportion of men with HIV infection had multiple lesions, and the lesions were more likely to be caused by syphilis.