Growth hormone (GH) appears to play a major role in a reciprocal axis that has been postulated between the thymus and pituitary glands. Our previous studies showed that thymic structure, as well as T-cell proliferation and IL-2 synthesis, could be restored in aged female Wistar-Furth rats by the implantation of GH3 pituitary adenoma cells. These cells secrete GH and some prolactin. We have now used three different approaches to determine whether GH affects a variety of immune events in vivo in both old and young rodents, and whether GH3 cells can directly affect progenitor T-cells in nude rats that congenitally lack a thymus gland. To test the effects of GH in aged rats, 750 pg of pituitary-derived ovine GH was injected 2 X daily into 26-month-old Fischer 344 rats for 5 weeks. This approach demonstrated that GH augments splenocyte proliferation to T-cell lectins as well as natural killer (NK) activity at low effector:target ratios even though morphologic characteristics of the thymus were not altered. To assess the effect of GH in young rodents, mice were studied that were transgenic for the rat metallothionein-GH gene. Histologic evaluation of thymus glands revealed that the amount of adipose tissue and the number of epithelial cells and Hassall's corpuscles are augmented in transgenic mice. Splenocyte proliferation at suboptimal mitogen doses is greater in transgenic than in control littermate mice, but neither IL-2 synthesis nor antibody synthesis to sheep erythrocytes is affected. The role of pituitary hormones on progenitor T-cells was then explored by implanting GH3 cells into Rowett nude rats. GH3 cells are unable to augment proliferation to T-cell lectins, IL-2 synthesis, antibody production to sheep erythrocytes, or NK activity in nude rats. Collectively, these experiments show that T-cells and NK cells from aged rats are not inherently defective because their proliferative responses to lectins and cytolytic activity can be augmented by exogenous GH. If GH affects progenitor T-cells, these effects are not apparent in nude rats. Finally, GH can also augment T-cell proliferative responses in young rodents, but the immunoenhancing effects are not as apparent as those observed in immunocompromised aged animals.