Previous studies in several species have indicated that immune function declines with age and that thyroid hormone is required for the maintenance of normal immune competence. Other data suggest that tissue responsiveness to thyroid hormone decreases with age, raising the possibility that the age-related decline in immune competence is the consequence, at least partly, of a decrease in the response to thyroid hormone. We propose to explore the latter hypothesis, in the rat, using as response indices several metabolic functions, that have been shown to be necessary for or related to lymphocyte transformation induced by mitogenic agents and that we have shown to be stimulated by thyroid hormone in vitro. First, we will study the in vitro activities of these metabolic functions and their stimulation by triiodothyronine in lymphoid tissue from animals of varying age. We also propose to examine the age-related response of these functions, measured in vitro, to changes in thyroid status in vivo. We propose, in addition, to examine whether the decline with age in the mitogenic response of the lymphoid tissue is accompanied by an impaired metabolic response to mitogenesis, and whether these responses are altered by changes in in vivo thyroid status.