OBJECTIVE We investigated preoperative and postoperative serum alpha-subunit levels and the alpha-subunit response to TRH in patients with various types of pituitary tumour and correlated the data with histological findings in order to clarify the significance of alpha-subunit measurement in pituitary adenomas. PATIENTS We examined 59 patients with pituitary tumours (22 with GH cell adenomas, 30 with clinically nonfunctioning adenomas and seven with other tumours) treated at Toranomon Hospital between 1996 and 1998. RESULTS The basal alpha-subunit level was supranormal in six out of 22 (27%) patients with a GH cell adenoma and in nine out of 30 (30%) patients with a nonfunctioning adenoma. A paradoxical alpha-subunit response to TRH was found in seven out of 22 (32%) patients with a GH cell adenoma. These seven patients also showed a paradoxical GH response to TRH administration. In addition, paradoxical response to TRH was found in eight out of 30 (27%) patients with a clinically nonfunctioning adenoma. In contrast, patients with other types of pituitary tumour showed neither a supranormal alpha-subunit level nor a paradoxical response to TRH. The supranormal alpha-subunit level and the abnormal response to TRH were normalized in both GH cell adenoma and nonfunctioning adenoma patients after successful surgery. Immunohistochemical studies showed alpha-subunit positive cells in 51% of GH cell adenomas or nonfunctioning adenomas and there was a good concordance with the serum alpha-subunit levels in both GH cell adenoma and nonfunctioning adenoma patients. CONCLUSIONS These findings suggest that supranormal serum alpha-subunit levels are mainly due to hypersecretion by the tumour itself, while the paradoxical alpha-subunit response to TRH is an associated phenomenon in patients with a GH cell adenoma or nonfunctioning adenoma. The alpha-subunit level and the response to TRH may be useful indicators for assessing the operative outcome, especially in nonfunctioning adenoma patients who have no other definite endocrine markers.