The serum glycoprotein hormone alpha subunit concentration was measured in 957 nonpregnant patients with benign disorders and 683 patients with unselected malignancies. Postmenopausal women had significantly higher alpha levels than premenopausal women or men. When the patients were subdivided according to age, sex or disease sites, significant population differences were found for women less than 50 years of age and patients with cancers of presumed neural crest origin. However, individual serum alpha levels in patients with benign disorders or malignancies demonstrated considerable overlap. No population differences in serum alpha concentrations were demonstrated between patients grouped according to stage of disease, suggesting that serum alpha were not directly related to tumor burden. Similarly, there was no statistical association between clinical improvement or deterioration and change in the serum alpha subunit concentration. These results indicate that measurement of the glycoprotein hormone alpha subunit concentration in the serum is not useful for screening patients for cancer or for monitoring the clinical course of patients with the vast majority of cancers.