Background: Because of the relative clinical inefficacy of antifungal therapy in the past, onychomycosis has largely been viewed as an incurable condition. The availability of two new oral antifungal agents suggests the possibility of revising this clinical precept. Objective: This study compared the efficacy and tolerability of terbinafine and itraconazole in the treatment of onychomycosis of the toenails. Methods: This investigation was a multicenter, double-blind, parallel group study. The primary therapeutic endpoints measured were mycologic cure and clinical improvement. Results: Mycologic cure rates (negative culture and microscopy) at the end of the study were 81% for terbinafine versus 63% for itraconazole (2p < 0.01). A total of 92% of terbinafine-treated patients had negative cultures at the end of the study, compared with 67% of itraconazole-treated patients (2p < 0.0001). Terbinafine was more effective than itraconazole in increasing the length of the unaffected area of the target nail: 9.44 mm versus 7.85 mm (2p < 0.05). Conclusion: Terbinafine is more effective than itraconazole in the treatment of toenail onychomycosis. (J Am Acad Dermatol 1998;38:S53-6.)