This investigation examined the role of ulcerative and non-ulcerative sexually transmitted diseases (STDs) in increasing susceptibility to HIV seroconversion in a large population of uninfected and predominantly heterosexual persons attending a New Orleans STD clinic. A retrospective cohort of clients with repeat HIV tests between January 1990 and April 1998 was constructed using three independent sources of information. Multivariate Cox regression was used to identify risk factors for HIV seroconversion while controlling for the effects of behavioral risk factors. A time-dependent covariate for STD allowed HIV seroconversion to be examined in relation to the timing of STD diagnosis. Having a recent syphilis or GUD diagnosis was associated with significantly increased hazards of seroconversion (among men: hazard ratio [HR], 4.2 [2.4-7.2]; among women: 5.0 [1.9-13.0]). Among men with no history of GUD or syphilis, those with recent gonorrhea within 1 year prior to seroconversion were 2.8 (1.5-5.2) times as likely to seroconvert. This study suggests that both ulcerative and non-ulcerative STD may be associated with increased risk of HIV transmission and therefore comprehensive STD control strategies may be particularly effective tools for HIV prevention.