beta-Adrenergic receptors (R) on several tumor lymphoid cell lines were characterized both directly by beta radioligand binding of 125iodo-cyanopindolol (125I-CYP) to intact cells and membranes, and functionally by assessing hormone-dependent changes in cyclic 3',5' adenosine monophosphate (cAMP) levels on intact cells and measuring adenylate cyclase (a.c.) activity on membranes. Only two lymphoid cell types, BW 5147 (a T cell derived lymphoma cell line) and TIB 221 (a B cell derived line) displayed significant amounts of beta-adrenergic R by 125I-CYP specific binding. Despite this, no stimulation of the a.c. activity was found in the presence of beta-adrenergic agonists in these cells in comparison with native lymphocytes or cells of the well-known S49 cell line used as a positive control. beta-Adrenoceptor specific uncoupling was confirmed by aluminum tetrafluoride (AlFl4) direct activation of the a.c. system in the beta R-bearing cell membranes and by an increase in cAMP production induced by PGE1, another hormone that activates the a.c. Structural characterization of beta-adrenoceptors by photoaffinity-labeling demonstrates that uncoupling was not due to a structural alteration of the beta-adrenergic R expressed in these lymphoma cell lines, as these R gave similar results as native or S49 cells. It can be concluded that functional beta-adrenoceptors are absent in these lymphoma cells. The possible implication of alternative transmission pathways and original neuroendocrine control in tumor lymphoid cells is discussed.