Whether griseofulvin, which pioneered oral antifungal therapy, works topically has long been an open question. The effectiveness of a 1% griseofulvin spray formulation and the vehicle alone against experimentally induced Trichophyton mentagrophytes lesions on the forearms of 16 healthy volunteers and in the treatment of 100 tinea pedis patients (various dermatophytes) was evaluated in a double-blind study. After treatment of the 58 induced lesions twice daily for 14 days with topical griseofulvin (28) or placebo (30), 89% of lesions receiving griseofulvin were mycologically negative compared with 30% in the placebo group (P < 0.0001). In the tinea pedis patients who applied medication once daily for 4 weeks the mycological cure was 79.2% on the fourth week and 80.9% 2 weeks post-treatment. Resurgence of dermatophytes quickly followed the end of treatment in the placebo group only, which had a mycological cure rate of 34% (week 6). Administration of a topical formulation of griseofulvin thus may be an effective treatment for interdigital dermatophyte infections.