The therapeutic efficacy of a topical antifungal ointment containing 2% tolnaftate was studied in a guinea pig model of tinea pedis using the following four topical antifungal preparations commercially available as reference drugs: variotin (3,000 U/g ointment); phenyl-11-iodo-10-undecynoate (0.5% ointment); siccanin (1% ointment); and clotrimazole (1% cream). After the infection fully developed, the infected animals were treated twice daily with the testing drug or reference drug for consecutive four weeks. Therapeutic efficacy was mainly evaluated on the basis of the extent of the yield of fungal cultures from the infected skin tissues (infection intensity) at the end of the treatment period. In animal groups treated with tolnaftate as well as with three reference drugs, siccanin, phenyl-11-iodo-10-undecynoate and clotrimazole, the average infection intensity was significantly lower than that for untreated control group (P < 0.05-0.005) although no culture-negative animal was seen in any treated animal group. Comparing with all the reference drugs, tolnaftate was the most highly effective and there was significant difference in the average infection intensity between a tolnaftate treated and each reference drug-treated groups (P < 0.01-0.005). These results confirm the clinical usefulness of the current tolnaftate preparation in the treatment of patients with tinea pedis and probably other clinical forms of dermatophytoses.