The adherence of clinical isolates of Staphylococcus aureus to cultured mouse epidermal cells was studied. Adherence of the isolates to the cells varied from strain to strain. When epidermal cell differentiation was induced by raising the calcium concentration in the medium, three out of 10 strains tested adhered better to calcium-induced differentiated cells than to undifferentiated cells, and one strain demonstrated higher adherence to undifferentiated cells than to differentiated cells. No significant difference between the adherences to both types of epidermal cells was observed with the other six strains. No relationship was observed between adherence and surface hydrophobicity with bacterial cells. Lipoteichoic acid and N-acetyl sugars caused limited inhibition of adherence. The adherence assay method employed in this study is useful for investigating the effects of epidermal cell differentiation on bacterial adherence in vitro.