Proopiomelanocortin (POMC) is a precursor polypeptide for various bioactive peptides, including adrenocorticotropic hormone, alpha-, beta-, and gamma-melanotropin, beta-endorphin, and beta-lipotropin. Although the classical source of POMC is the pituitary, various studies indicate the expression of POMC in several nonpituitary tissues. In this study, in situ hybridization with anti-sense cRNA riboprobe was used to show expression of POMC mRNA in human epidermis and cultured human epidermal cells (melanocytes and keratinocytes). POMC mRNA was amplified by reverse transcriptase-polymerase chain reaction using anti-sense and sense primers designed from Exons 2 and 3 of POMC gene. A approximately 300 bp product was present in normal human skin, grafted human skin, and cultured normal human melanocytes and keratinocytes. By Southern analysis this product was hybridized specifically to the POMC cDNA. Sequence analysis of the reverse transcriptase polymerase chain reaction product from tissues or cells showed 85% homology to POMC cDNA from human, bovine, pig, and monkey sources. This suggests the existence of a putative isoform or variant of POMC mRNA in human epidermis.