Epidemiologic, clinical, and microbiologic data were collected from 299 men with nonsyphilitic genital ulcer disease. One hundred eighteen (39%) were culture-positive for Haemophilus ducreyi, 57 (19%) were culture-positive for herpes simplex virus, and 124 (41%) were culture-negative. Patients with chancroid were significantly more likely than those with genital herpes to have been frequent users of alcohol (44% vs. 23%, P = .006). They were also more likely recently to have used cocaine (25% vs. 9%, P = .013), had sex with a prostitute (17% vs. 5%, P = .035), traded drugs for sex (16% vs. 2%, P = .005), and had a sex partner who used drugs (38% vs. 13%, P = .001). Culture-negative patients were similar to chancroid patients with respect to most epidemiologic risk factors. Despite the epidemiologic similarities, the clinical features of culture-negative ulcers resembled those of culture-proven herpes ulcers more closely than they did those of culture-proven chancroid ulcers. These data establish a link between chancroid in the United States and the use of crack cocaine.