A total of 304 patients with a clinical diagnosis of palmar-type tinea pedis or manus and a positive mycologic examination were recruited into this double-blind, randomized, multicenter, phase III study. Patients were randomized to receive either oral itraconazole 200 mg twice daily (in the morning and evening) for 7 days, followed by placebo for 7 days (n = 153), or placebo in the morning and oral terbinafine 250 mg in the evening for 14 days (n = 151). At the first visit and 1, 2, and 6 weeks after the start of the study, signs and symptoms were assessed clinically, and scales were taken for mycologic assessments (microscopy and culture). At weeks 1, 2, and 6, the effectiveness of therapy was evaluated globally and given a rating of healed (absence of signs and symptoms), marked improvement (> or = 50% clinical improvement), considerable residual lesions (< 50% clinical improvement), no change, or worsened. The primary efficacy parameter was the mycologic cure rate at the follow-up end-point (week 6). The tolerability of the study medications was assessed at weeks 1 and 2. Adverse events were recorded at weeks 1, 2, and 6. Routine hematologic and biochemical tests were performed at the start of the study and after 1 week of treatment. No significant differences were seen in the baseline patient characteristics between the two groups. The rate of mycologic cure (negative microscopy and culture test result) was 79% in the itraconazole group and 80% in the terbinafine group at the follow-up end-point. The analysis of the 90% confidence interval for the difference between the treatment groups (-7.1, 5.4) and the outcome of the Blackwelder test (for two one-sided tests, P = 0.013 and P = 0.029) showed the two treatments to be equivalent. The results of the global evaluations of the efficacy in the two treatment groups are shown in Table 1. The rate of clinical response (healed or markedly improved) was 93% in the itraconazole group and 91% in the terbinafine group at the follow-up end-point. The analysis of the 90% confidence interval for the difference between the two groups (-2.5, 5.7) and the outcome of the Blackwelder test (for two one-sided tests, P = 0.004 and P < 0.001) showed the two treatments to be equivalent. The severity of the clinical signs and symptoms decreased from the baseline to the treatment end-point and from the treatment end-point to the follow-up end-point in both groups. At the double-blind treatment period end-point (week 2), the tolerability of the study medication was rated as very good or good in more than 97% of patients. During treatment, 21 of 153 patients (14%) in the itraconazole group and 28 of 151 patients (19%) in the terbinafine group reported adverse events. During follow-up, one patient in the itraconazole group and two in the terbinafine group reported adverse events. The most frequent events were headache, abdominal pain, nausea, vomiting, and hypertriglyceridemia. Two patients in the itraconazole group and four in the terbinafine group withdrew because of adverse events. Severe adverse events were reported by one patient in the itraconazole group and five in the terbinafine group. Serious adverse events were reported by two patients in the terbinafine group, although these were probably not drug related. No clinically relevant changes in laboratory variables were observed.