BACKGROUND: Ciclopirox olamine (CPO) is a broad-spectrum antifungal with anti-inflammatory properties effective against the yeast implicated in seborrhoeic dermatitis, Malassezia spp. This study compared 1.5% CPO shampoo with 2.0% ketoconazole shampoo and placebo in scalp seborrhoeic dermatitis. METHODS: A randomized, double-blind, 4-week treatment period was preceded by a 2-week run-in period and followed by a 2-week run-out period. A total of 350 patients (150 CPO, 150 ketoconazole, 50 placebo) were enrolled. Assessments included scalp area affected, the severity of scaling, erythema, itching and scaling, and overall signs and symptoms. RESULTS: Both shampoos were significantly more effective than placebo in reducing the area affected. The mean reduction from baseline to end of treatment was 48.2 cm(2) with CPO, 41.4 cm(2) with ketoconazole and 20.0 cm(2) with placebo. Patients rated the CPO shampoo as superior to placebo (p<0.001) and ketoconazole shampoo (p<0.05) on the basis of overall signs and symptoms. Assessments of itching and scaling were also significantly in favour of the CPO shampoo over placebo at the end of treatment. All three shampoos were well tolerated. CONCLUSIONS: CPO shampoo was superior to placebo and at least as effective as ketoconazole shampoo in treating scalp seborrhoeic dermatitis. Patients rated the overall improvement as better with CPO than with ketoconazole shampoo.