The etiology of genital ulcer disease was determined in 210 consecutive patients (110 men and 100 women) who presented at a clinic in Kigali, Rwanda, because of genital ulcers. When mixed infections are included, syphilis (21%), chancroid (24%), and genital herpes (17%) were about equally frequent in men. Lymphogranuloma venereum with ulceration was found in 11% of patients. Syphilis (40%) was the most common diagnosis in women; genital herpes (20%), lymphogranuloma venereum with ulceration (19%) and chancroid (12%) also were frequent diagnoses. Microscopic examination for treponemes after silver-impregnation staining had a poor sensitivity and specificity for the diagnosis of primary syphilis. Overall, 59% of the patients (43% of the men and 77% of the women) had IgG antibodies to the human immunodeficiency virus.