Topical antimicrobial agents are essential to optimal burn care. However, exposure of WI-38 human diploid fibroblasts (ATCC CCL 75) and fresh donor human dermal fibroblasts to silver sulfadiazine and mafenide acetate results in a significant reduction in cell proliferation, as determined by hemocytometer cell counts and total matrix protein assays, within 48 hr of exposure. Changes in cellular morphology and progressive deterioration of cytoplasmic organelles and the nucleus are seen with phase-contrast microscopy and transmission electron microscopy. These findings may explain the clinical observation of delayed wound healing after the use of topical antimicrobial agents.