We report the sensitivity and specificity of physical examination findings for diagnosing primary syphilis, chancroid, and genital herpes. The physical features of genital ulcers in 446 men were measured in accordance with a quantitative scale. Two hundred-twenty of these men had an established, single microbiological diagnosis. Forty-five (20%) had primary syphilis, 118 (54%) had chancroid, and 57 (26%) had genital herpes. There was considerable overlap in the clinical presentation of these three diseases. The classic clinical sign complex attributed to primary syphilis (painless, indurated, clean-based ulcers) was only 31% sensitive but 98% specific. The classic presentation of a chancroid ulcer (a deep, undermined, purulent ulcer) was only 34% sensitive but 94% specific. The classic description of genital herpes ulcers (multiple, shallow, tender ulcers) was only 35% sensitive but 94% specific. Inguinal lymph node findings did not contribute significantly to clinical diagnostic accuracy. These data indicate that the clinical diagnosis of genital ulcer disease can be made with reasonable certainty only for a minority of patients. Rapid, sensitive, and specific diagnostic tests for syphilis, chancroid, and genital herpes are needed.