Corynebacterium acnes strains cross-resistant to clindamycin and erythromycin were observed following long-term selection or mutagenic treatment in the laboratory. Similar strains were found among clinical isolates from patients using clindamycin or erythromycin topically in the treatment of acne vulgaris. Clindamycin resistance was never observed in the absence of resistance to macrolides or other lincosaminides. It is suggested that this resistance may result from an alteration of the 50S ribosomal subunit.