A subset of growth-hormone (GH) producing pituitary adenomas harbour mutations at residues Arg201 and Gln227 of the alpha subunit of the stimulatory G protein (G(s) alpha). One such mutation has been reported in a GH-producing tumour from a patient with multiple endocrine neoplasia type 1 (MEN 1) although mutations have not been reported in other tumours associated with MEN 1. We used PCR-induced restriction site analysis to screen for these mutations in 80 tumours of the pituitary, parathyroid and endocrine pancreas. Arg201 mutations were detected in 1 non-functioning and 4 GH-producing pituitary tumours. No mutations were found in any of the endocrine tumours tested at Arg179 of the G(i2)alpha subunit, a homologous residue to Arg201 of G(s) alpha. Our results indicate oncogenesis in the majority of pituitary and parathyroid tumours is independent of mutations of G(s) and G(i2) alpha. (C) 1995 Academic Press, Inc.