The three major diseases characterized by genital ulcers--genital herpes, syphilis, and chancroid--are common, with genital herpes being most common in industrialized countries and chancroid being most common in developing countries. One fourth to one half of patients with genital ulcers have no diagnosed cause for their illness despite diagnostic efforts. The bulk of these cases is probably constituted by one of the three diseases for which diagnostic tests are falsely negative. There is accumulating evidence that genital ulcers facilitate the transmission of human immunodeficiency virus (HIV), and they may also be markers of high-risk behavior for acquisition of HIV. Appropriate therapy of patients with genital ulcers (as well as their sexual partners) depends on accurate diagnosis. Patients with genital ulcers, particularly those with syphilis or chancroid, should be encouraged to undergo testing for HIV infection.