The purpose of this study was to elucidate the cellular basis for growth hormone deficiency in Lewis-derived dwarf rats. To this end, we used reverse hemolytic plaque assays to evaluate hormone release. This allowed us to determine the proportional abundance of GH- and PRL- secreting cells and estimate the relative amount of hormone secreted by individual pituitary cells from dwarf rats and their somatically normal counterparts. The percentage of all pituitary cells that released GH (formed plaques) in pituitary dispersions was substantially lower for dwarfs when compared with normals in the absence (3.8 +/- 2.2% vs. 43.4 +/- 2.2%) or presence (6.6 +/- 3.8% vs. 45.7 +/- 1.4%; n = 3) of GRF. In addition, GH secretors from dwarfs released less hormone (formed smaller plaques) than their normal counterparts under both basal and stimulated conditions. An analysis of the relative number of GH cells that formed plaques of various sizes was accomplished by constructing a frequency distribution. Dwarf GH secretors formed more small plaques and proportionately fewer larger plaques than normals under both basal and stimulated conditions. For comparison, we also quantified the proportions of PRL secretors and found that they were actually more abundant in dwarfs than normals in the absence (52.4 +/- 4.6% vs. 33.7 +/- 3.7%) or presence (53.4 +/- 4.9% vs. 33.8 +/- 4.1%; n = 4) of TRH. Treatment with this secretagogue consistently increased mean PRL-plaque area for both groups. Our findings demonstrate that dwarf rats are severely deficient in the proportion of GH secretors. In addition, the few GH secretors present in the dwarf pituitary were less responsive to GRF than normals. In contrast, PRL cells in dwarfs appear to be functionally similar to those of their normal counterparts. The reciprocal relationship in the proportions of GH and PRL secretors in dwarfs provides a rather unique model for investigating the functional relationship between these cell types.