Several agents are known that can elevate cyclic AMP levels in lymphoid cells, e.g. isoproterenol, PGE1 and adenosine. We have studied the cyclic AMP increasing effect of these agents on thymocytes from mouse and man and on human peripheral T lymphocytes. In contrast to mouse thymocytes and human peripheral T lymphocytes, human thymocytes appeared to be insensitive to isoproterenol, but did respond to PGE1 and adenosine. Furthermore, the density of beta-adrenergic receptors on the cells was determined by measuring the specific binding of 3H-dihydroalprenolol. A correlation was found between the receptor density on the cells and the rise in intracellular cyclic AMP induced by isoproterenol: human thymocytes appeared to have very few beta-adrenergic receptors, in contrast to thymocytes from mouse or to T lymphocytes from human blood. We conclude that the development of beta-adrenergic receptors in T cell ontogeny is different for mice and human beings. Comparison of animal models with the situation in man should be made with caution.