Isolated hypersecretion of the alpha subunit of the glycoprotein hormones occurred in two men with previously diagnosed "nonfunctioning chromophobe adenomas." The alpha hypersecretion was unresponsive to hypothalamic releasing hormone, thyroid hormone, and sex-steroid hormones. After trans-sphenoidal surgery and conventional pituitary irradiation, alpha secretion was decreased. Increased quantities of immunologically active and biologically inactive luteinizing hormone (LH) material were detected in serum and in tumor homogenate. Immunologic and gel-chromatographic studies determined that only the alpha subunit was present and that it was cross-reacting in the LH immunoassay. These studies suggest that the alpha subunit may be a useful marker of pituitary tumors, particularly in patients without clinical evidence of hormonal hypersecretion.