BACKGROUND: Antibiotics are often combined with other agents to provide topical acne treatments that are effective against both inflammatory and non-inflammatory lesions and minimize the development of antibiotic resistance. OBJECTIVES: To compare the clinical effectiveness of two combination treatments for facial acne: a ready mixed, once daily gel containing clindamycin phosphate (1%) plus benzoyl peroxide (5%) (CDP + BPO) and a twice daily solution of erythromycin (4%) plus zinc acetate (1.2%) (ERY + Zn). METHODS/PATIENTS: In this assessor-blind, randomized study, 73 patients were treated with CDP + BPO once daily and 75 patients with ERY + Zn twice daily. The treatment period was 12 weeks and lesion counts and global improvement were assessed at weeks 1, 2, 4, 8 and 12. RESULTS: CDP + BPO showed an earlier onset of action with a faster significant reduction in total lesion counts than ERY + Zn. The proportion of patients with at least a 30% improvement in non-inflammatory lesions at week 1 was 31.5% for CDP + BPO and 17.3% for ERY + Zn; the corresponding percentages for inflammatory lesions were 39.7% and 29.3%. A difference was also observed at week 2 (53.4% vs. 36.0% for non-inflammatory lesions and 72.6% vs. 53.3% for inflammatory lesions). The trend in favour of CDP + BPO, although less marked, continued to the end of the study, with reductions in the total lesion count at endpoint of 69.8% for CDP + BPO group and 64.5% for ERY + Zn group. Both treatments were well tolerated. CONCLUSIONS: CDP + BPO and ERY + Zn are effective treatments for acne but CDP + BPO has an earlier onset of action that should improve patient compliance.