Cutaneous fungal infections in immunocompromised patients can be aggressive and difficult to treat. To determine the safety and efficacy of oral terbinafine for the treatment of tinea corporis or tinea cruris in subjects with human immunodeficiency virus (HIV) infection or diabetes, 2 prospective, randomized, open-label studies were conducted in general community and referral centers. HIV-positive (n = 6) and diabetic patients (n = 8) between the ages of 18 and 75 years diagnosed with either tinea corporis or tinea cruris, as confirmed by potassium hydroxide (KOH) wet mount microscopy, were randomized to receive either 1 or 2 weeks of the antifungal treatment. Patients received oral terbinafine 250 mg once daily for 1 or 2 weeks. Main outcome measures were mycological cure, determined at week 6 for HIV-positive and diabetic patients. Three subjects were excluded from the efficacy analyses because of negative cultures at screening (n = 2) and lack of follow-up cultures (n = 1). Efficacy results were similar between the 1- and 2-week groups in both studies. All HIV-positive subjects and 83% of diabetic subjects achieved mycological cures at week 6 based on culture results. In a safety population that included all randomized patients (N = 14), no subject experienced adverse events or significant changes in laboratory findings related to study medication. Results of these small series indicate that a short course of oral terbinafine 250 mg once daily is a safe and effective treatment for tinea corporis or tinea cruris in subjects with HIV infection or diabetes.