The stimulation or inhibition of adenylate cyclase by hormones and chemicals is mediated by the stimulatory or inhibitory guanine nucleotide-binding proteins, Gs and Gi respectively. Although the presence of these G-proteins in the epidermis has been suggested, no direct information regarding their nature has been available. Using cDNAs for these G-proteins as a probe, we investigated the nature of the G-proteins of various keratinocytes. FRSK cells, a cell line derived from fetal rat epidermal cells, and SV-40-transformed human epidermal cells, both of which are highly proliferative keratinocytes, contained mRNAs for both Gs-α and two Gi-α proteins (Gi-2α and -3α). No evidence for the presence of Gi-1α or Go-α was obtained. Normal human or pig epidermis had a relatively small amount of mRNAs for these G-proteins in the stable (hypoproliferative) condition. Tape-stripping-induced, and UVB-induced hyperproliferative epidermis contained an increased amount of these G-protein messages. However, all Gs-α, Gi-2α and -3α, as well as Β-actin mRNAs, were increased to a similar extent, and no specific expression of G-protein messages could be detected in the hyperproliferative epidermis. © 1990 Springer-Verlag.