Plasma and pituitary concentrations of LH, FSH and prolactin (Prl) were compared by radioimmunoassay (RIA) in young mature (2–4 monthold) and aged (16–22 month-old) female C57BL/6 mice, following various experiments with IP injections of GnRH. Unanesthetized mice were bled by cardiac puncture either (1) at various time intervals following a single injection of 25 ng GnRH, (2) after several injections of 25 ng GnRH, or (3) after receiving excessively large doses of GnRH. From the RIA of plasma and pituitary concentrations of LH, it appeared that the pituitaries of aged mice were, in general, capable of responding to GnRH treatment, only to a lesser degree than that of the younger females. The exception was that the pituitaries of aged mice that were subjected to unusually high doses of GnRH continued to secrete higher levels of LH, whereas the response of the pituitaries in younger mice plateaued after receiving 25 ng GnRH. Plasma and pituitary concentrations of FSH and Prl remained fairly constant when aged GnRH-treated females were compared with aged controls. This was also true when FSH and Prl concentrations in the younger mice were compared with their controls, except for significantly higher plasma FSH and significantly lower pituitary FSH following several injections of GnRH. When the hormonal concentrations of the young and aged groups were compared in the various experiments, the older mice consistently exhibited higher levels of gonadotropin and lower levels of prolactin than those of the younger mice. In a separate experiment, in which a radioreceptor assay (RRA) was used to quantitate plasma LH in GnRH-treated mice, both age groups were found to have lower concentrations of LH ( p<0.05) than those obtained by RIA from the same animals. The RRA to RIA ratio, however, was 0.84 for 2–4 month-old and 0.57 for 16–22 month-old mice. These studies suggest that the anterior pituitary of the aged mouse is less sensitive to GnRH stimulation.