In Africa, establishment of an accurate clinical diagnosis in cases of genital ulcer disease is difficult owing to atypical presentation of ulcerations and mixed infections. This is compounded by the frequent lack of suitable laboratory facilities. In 240 cases of genital ulcer disease among mineworkers in Carletonville, South Africa, this study endeavored to correlate the clinical diagnosis with laboratory findings. Clinical accuracy and positive and negative predictive values were determined for each type of genital ulcer disease encountered. Overall, the accuracy of clinical diagnosis was 68% for single infections, 80% for chancroid, 55% for primary syphilis, 27% for lymphogranuloma venereum (LGV), and 22% for genital herpes. Adequate laboratory facilities are indispensible for the establishment of an accurate etiologic diagnosis of genital ulcer disease and thus the institution of appropriate antimicrobial therapy.