It is not known whether enhanced growth hormone (GH)-releasing factor (GRF)-stimulated GH release observed in the male reflects differences in somatotrope numbers and/or secretory response to GRF. We addressed this question by using the hemolytic plaque assay which allows quantification of hormone secretion by single pituitary cells. Time-course studies and GRF-GH concentration-response relationships (0.01, 0.1, 1, 10, 100, 1,000 nM GRF) in age-matched male and diestrous day 2 female rats were compared by quantitating the percent of GH plaque-forming cells, and measuring the plaque areas. The male pituitary contained a greater percent (P less than 0.05) of somatotropes (% of plaque-forming cells 45 +/- 2 vs. 27 +/- 4% in the female; mean +/- SE). GRF induced a greater concentration-dependent increase in plaque areas in the male. Maximal responses were attained at 10 nM GRF in both sexes. However, mean maximal plaque area was significantly greater (P less than 0.001) and the EC50 was significantly lower (P less than 0.05) in the male (0.25 +/- 0.09 vs. 1.78 +/- 0.64 nM in the female). The data suggest that the greater percent of somatotropes in the male and greater secretory capacity and sensitivity to GRF may contribute to sex-related differences in GH secretion in the rat.