The glycoprotein hormone alpha-subunit is secreted as a free molecule as well as a molecule combined to a glycoprotein hormone beta-subunit. In human subjects, plasma levels of the free alpha-subunit were measured by means of a specific radioimmunoassay. Plasma concentrations were high during the neonatal period, then decreased to a nadir at the age of 6 years. A significant pubertal increase occurred in both sexes, more pronounced in girls. In female subjects mean levels (+/- SEM) were 0.21 +/- 0.05 before puberty and 0.51 +/- 0.03 ng 1 degrees IRP-hCG alpha/ml in follicular phase. During menstrual cycle, a typical preovulatory surge was seen simultaneous with the LH surge. During aging, plasma levels increased slowly in males, abruptly in menopausal females. The pituitary reserve as assessed by LH-RH stimulation test (100 micrograms i.v./m2) exhibited a significant pubertal maturation in boys and girls. Chronic administration of LH-RH agonist induced a marked increase of alpha-subunit levels, whereas LH levels were deeply suppressed. LH-RH injections in children treated for precocious puberty with a LH-RH agonist induced a significant release of alpha-subunit despite an almost complete abolition of LH release. In conclusion, from a quantitative point of view, the glyco-protein hormone alpha-subunit is a major secretory product of the pituitary. It seems that there is a specific regulation of its secretion, resembling but not identical to LH secretion regulation. Whether or not it plays a biological role remains uncertain.