Two studies on the pharmacokinetics of fluconazole in skin and nails are reported here. In 1 study, 12 healthy volunteers received fluconazole 50 mg once daily for 12 days and 11 healthy volunteers received fluconazole 150 mg once weekly for 2 weeks. Fluconazole assays were performed on samples of serum, stratum corneum, dermis-epidermis, and eccrine sweat. In a second study, 36 patients with toenail onychomycosis received either fluconazole 150 mg once weekly or griseofulvin 1000 mg once daily for 12 months. Fluconazole assays were performed on nail clippings and serum samples from the patients receiving fluconazole. Tissue concentrations of fluconazole regularly exceeded plasma concentrations in these studies. In the skin study, the highest concentrations were achieved in stratum corneum, with accumulation occurring up to the end of dosing. Subjects who received 50 mg once daily had higher levels of fluconazole in stratum corneum, sweat, and epidermis-dermis than those subjects who received 150 mg once weekly. In the toenail study, fluconazole concentrations increased for the first 6 months, reaching levels much higher than serum concentrations (P < .001), with no significant difference between healthy and diseased nails.