There is growing evidence that changes in hormone secretion during aging can alter some functions of the thymus. In order to identify further relationships between changes in endocrine and thymic function during aging we measured the circulating levels of prolactin (PRL), growth hormone (GH) thyrotropin (TSH) thyroxine (T4) and triiodothyronine (T3), and determined their relation to a number of T lymphocyte functional indices in 20 young (4 months) and 20 old (28-30 months) Long-Evans male rats. Half of the young and old rats were chronically cannulated in order to obtain sequential plasma samples for measuring PRL, GH and TSH by RIA. Total T4 and T3 were measured by RIA in the trunk serum of all animals. Thymus and spleen cell cultures from each rat were established and used to assess the ability of thymocytes to respond to mitogens and lymphokines as well as to measure the levels of IL-2 production by splenic lymphocytes. Mean plasma GH and serum T4 were significantly lower in old as compared to young rats (P < 0.05 and P < 0.001 for GH and T4, respectively), while PRL, TSH and T3 did not show significant age changes. Thymic cell number showed a 100-fold decrease in old as compared to young animals (10.6 +/- 3.0) X 10(6) vs. (898 +/- 98) X 10(6) cells, respectively) whereas no age change was detected in spleen cell numbers. The proliferative response of thymocytes exposed to Con A, IL-1, Con A + IL-1 or Con A + IL-2, was consistently higher in young than in old animals while the capacity of splenocytes to release IL-2 in response to Con A was not statistically different in young and old rats. The age changes in serum T4 showed a significant correlation with those in thymocyte count as well as with those in IL-1 + Con A- and IL-2 + Con A-induced thymocyte proliferation. Plasma GH showed a significant inverse correlation with splenocyte IL-2 release. Our results suggest, although do not prove, that the lower T4 and GH secretion that typically develops in old rats may play a causal role in some of the changes that occur in thymic-dependent functions during aging.