Erythromycin with or without additional zinc acetate is used topically in the treatment of acne vulgaris. A potential effect of zinc on the stratum corneum penetration of erythromycin was investigated in human volunteers. Skin surface washings and tape strippings from the skin of the back were collected after drug applications in 12 subjects for quantification of erythromycin levels. Zinc acetate increased the amount remaining on the back skin at 6 h after application from 40 ± 19 to 56 ± 15% of the dose and, vice versa, reduced the amount in stratum corneum strips from 22 ± 7 to 18 ± 7%, both with statistical significance. The effect varied with body region. Zinc acetate thus provided to prolong the residence time of erythromycin on the skin.