Since the heterosexual transmission of HIV may be enhanced in the presence of other sexually transmitted diseases (STDs), high STD prevalences in some African populations may contribute substantially to the HIV epidemic, but the magnitude of this effect is uncertain. A stochastic simulation model, SimulAIDS, was extended, and used to simulate the transmission dynamics of HIV infection and of ulcerative and non-ulcerative STDs in an attempt to mirror the development of the HIV epidemic in a rural population cohort of 10,000 under study by the MRC Programme on AIDS in Uganda. Three scenarios were compared, assuming different STD cofactor effects. Simulation results were most consistent with empirical data for a scenario that assumed enhancing effects on HIV transmission per sexual contact of 100 for ulcerative STDs and S for non-ulcerative STDs in females. A scenario assuming no STD cofactor effects was not consistent with results from the study population. By sampling from the simulated population, it was possible to assess the influence of various factors on associations between HIV and other STDs in observational studies. The most important included type of study design, choice of study sample, prevalence of STDs, misclassification of STDs, period over which STD history is recorded, and sexual behaviour characteristics. Further simulations were conducted to estimate the fraction of HIV infections in this population attributable to the cofactor effect of STDs, and to assess the relative effectiveness of differing intervention strategies. Results were consistent with STDs playing a critical role in establishing an HIV epidemic, their role decreasing as the epidemic progresses. Reducing the incidence of HIV infection in short-term sexual partnerships, through improved STD treatment, increased condom use, and a reduction in one-off sexual encounters, was found to have a substantial impact on HIV incidence in the general population.