The effects of human pancreatic GH-releasing factor-40 (hpGRF-40; 0.01-100 nM) and (Bu)2cAMP (0.015-1.5 mM) on GH release from primary monolayer cultures of pituitary cells were evaluated in rats of three age groups: postnatal days 2 and 12, and young adult males (3-4 months). Both hpGRF-40 and (Bu)2cAMP elicited a dose-related increase in GH release in cell cultures from each age group. However, the magnitude of the fractional increase over basal release was markedly age dependent. hpGRF-40-stimulated GH release (expressed as a percentage of control values) was greater in cultured cells of 2-day-old than of 12-day-old rats, which was, in turn, significantly greater than in cells of adult rats (P less than 0.001). Maximum hpGRF-40-stimulated GH release was 1058 +/- 50% of control values (+/- SE) in 2-day-old, 617 +/- 21% of control values in 12-day-old, and 405 +/- 6% of control values in adult pituitary cell cultures. The slopes of the dose-response curves differed significantly among the three age groups (P less than 0.001) and varied inversely with increasing age. GH release induced by (Bu)2cAMP was similarly age dependent; maximal stimulated release was 1073 +/- 20%, 414 +/- 4%, and 259 +/- 7% of control values in cultured cells of 2-day-old, 12-day-old, and adult rats, respectively (P less than 0.001 for age effect at each dose). As with hpGRF-40, the slopes of the dose-response curves for (Bu)2cAMP decreased with advancing age (P less than 0.001). Intracellular GH storage during culture, basal release of GH, and serum GH were also age dependent. Pooled serum GH was consistently elevated in 2-day-old rats (139 +/- 2 ng ml-1), became lower and more variable in 12-day-old rats (62 +/- 14 ng ml-1), and was even more variable in adult male rats (79 +/- 23 ng ml-1), owing to random sampling during spontaneous secretory pulses. These results indicate that the stimulatory effects of GRF and (Bu)2cAMP on GH secretion from cultured rat pituitaries vary with age; pituitary cells of newborn rats are relatively more sensitive to these secretagogues than those of adult rats. This increased responsiveness of the neonatal somatotroph to GRF may contribute to the elevation of the plasma GH concentration which is characteristic of the perinatal period in the rat.