The objective of this randomized, controlled, multicentre study was to assess the efficacy and safety of a topically applied retinaldehyde 0.1% gel in combination with a topical erythromycin 4% lotion for the treatment of acne vulgaris. Treatment consisted of applying either retinaldehyde or its vehicle every morning and erythromycin every evening for 8 weeks. Efficacy parameters were sequential lesion counts for papules and pustules, and a 6-point semiquantitative scale for comedones and microcysts. Safety parameters were local tolerance and adverse events. Of 74 recruited patients, 73 were appraisable for efficacy and safety. In both treatment groups, papules and pustules were reduced significantly at the end of treatment (P < 0.001), and no statistical difference was observed between the groups. Comedones and microcysts were significantly improved with retinaldehyde combined with erythromycin (P = 0.005), but not with erythromycin alone. However, no statistical difference between the groups could be demonstrated (test power, 50%). Local tolerance of the combined treatment group was very satisfactory, as only a few patients experienced local irritation. In conclusion, retinaldehyde combined with erythromycin appears to be a valuable topical therapy in polymorphic acne.