Considerable evidence indicates that the pituitary-gonadal axis is active in the fetus, but little is known about the relative times in development when the brain begins to secrete gonadotropin-releasing hormone (GnRH) and the hypophysis begins to secrete gonadotropin. The objective was to correlate the time of appearance of GnRH in the median eminence and organum vasculosum of the lamina terminalis (OVLT) with differentiation of LH-gonadotropes in the hypophysis of the fetal mouse by means of immunocytochemistry. Mice were studied at 15, 16, 17 and 19 days of gestation with the peroxidase-antiperoxidase (PAP) method of Sternberger, GnRH was first detected at 17 days of gestation in presumptive axons and axon terminals located adjacent to the superficial portal capillaries near the surface of the median eminence and close to the capillaries of the OVLT. LH-gonadotropes also were found initially at 17 days of gestation. They were prominent in the ventral half of the pars distalis. Most of these cells were ovoid or slightly angular, and almost all abutted one of the numerous sinusoidal capillaries present at this age in development. The number and staining intensity of both LH-gonadotropes and GnRH foci increased by 19 days. The close temporal relationship between the developmental appearance of GnRH and its target cell, the gonadotrope, provides further evidence that the potential for neuroendocrine control of gonadotropin secretion exists in the fetal mouse as early as 17 days of gestation.