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 (Gs 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 Gi2 alpha subunit, a homologous residue to Arg201 of Gs alpha. Our results indicate oncogenesis in the majority of pituitary and parathyroid tumours is independent of mutations of Gs and Gi2 alpha.