Glucocorticoid hormones are very potent inhibitors of keratinocyte proliferation. Their function is mediated by the glucocorticoid receptor (GR) which is highly expressed in mouse epidermis. In the study reported here we compared the effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and non-phorbol ester tumor promoters such as okadaic acid, chrysarobin, and benzoyl peroxide on the levels of GR protein and mRNA in SENCAR mouse epidermis. Glucocorticoid binding assay and Northern blot analysis revealed that all four tumor promoters decreased both GR protein and mRNA levels in keratinocytes in vivo. We also found that TPA and okadaic acid inhibited GR expression in keratinocyte cell line. These results suggest that GR inhibition may play an important role in mouse skin hyperplasia and promotion of skin carcinogenesis.