This study demonstrates the efficacy and safety of ketoconazole, a broad-spectrum oral antifungal agent administered to 20 patients with severe, extensive, and recalcitrant Trichophyton rubrum infection. The average patient has had continuous infection for 20 years. Sixteen patients had glabrous skin infection that encompassed an average of 40% of their skin surface. The remaining four patients had palmar-plantar infection. Ketoconazole was administered for 27 to 70 days in a daily oral dose of 200 or 400 mg. Initial clinical and mycological response occurred within five to seven days, and the glabrous and/or palmar-plantar skin changes improved at least 90% in all patients. In 13 of these patients, the infection cleared completely. The only side effects experienced--pruritus in four patients and photophobia in two patients--did not necessitate interruption of therapy. Overall, ketoconazole was found to be an effective and safe therapy for dermatophytosis. Follow-up examinations of our cases five months later showed recrudescence in 75% of them, which was not unexpected with these severe infections.