This study was designed to compare the efficacy and safety of sisomicin cream (0.1%) or mupirocin ointment (2%) in the treatment of primary or secondary pyodermas requiring topical antibiotic therapy alone. In the evaluable patients (n=290), impetigo was the commonest clinical condition reported. Staphylococcus aureus was the commonest pathogen isolated from the lesions. Both sisomicin and mupirocin treatments produced a steady improvement in the scores of erythema, oedema, vesiculation, pustulation, crusting and scaling but the improvement produced by sisomicin was quicker and more pronounced. The percentage of patients with complete clearing of all lesions was also higher with sisomicin than with mupirocin on days 4, 8 and 14. Patients subjectively rated the sisomicin formulation as excellent in 75% of cases as against 59% with mupirocin. Sisomicin and mupirocin are effective and safe in the management of pyodermas; however sisomicin therapy resulted in faster and greater relief of signs and symptoms.