Objective To investigate the incidence and clinical characteristics of gsp oncogene positive growth hormone-secreting adenomas of Chinese acromegalic patients. Methods Continuously 40 patients were studied. Serum hormone levels of pituitary and target glands were measured and growth hormone (GH)-TRH stimulating tests were done before transsphenoidal or transfrontal hypophysectomy. Deoxyribonucleic acid (DNA) was extracted from the frozen tumor tissue, and the DNA fragment encompassing codon 201 and 227 of the Gsα gene was amplified by polymerase chain reaction (PCR). Point mutations at codon 201 and 227 were detected using PCR direct sequencing method in order to get the incidence of gsp oncogene in GH secreting adenomas. Results Of 40 tumors studied, 22 (55%) were gsp positive. The point mutation from CGT(Arg) to TGT (Cys) at codon 201 was detected in 21 pituitary tumors, but the point mutation from CAG (Gln) to CTG (Leu) at codon 227 of the Gsα gene was found in only 1 tumor. All of the point mutations are heterozygous. The number of gsp positive patients which have 30% or more decrease of serum GH concentration after glucose inhibition is less than that of gsp negative patients (P=0.042). Compared to gsp negative patients, most of gsp positive patients showed paradoxical response to TRH stimulation (P=0.002). There were more gsp positive patients with the tumor diameter less than 25 mm (P=0.029) and with normal GH levels in OGTT after surgery (P=0.007). Conclusions Gsp mutation is one of the major intrinsic defects in the pathogenesis of growth hormone-secreting pituitary tumors and the identification of gsp mutation can be a reference for classification and prognosis of GH tumors.