We examined several cultured murine T cell lymphomas, induced by a radiation leukemia virus MuRadLV, including cell lines derived from immature T cells (5 clones of the BL/VL3 cell line), antigen-specific T helper cells (5 lines of the TL2 series), and one T cytotoxic cell line (NS8). With one exception (the TL2-9 cell line), these cells showed common characteristics: 1) an efficient adenylate cyclase system; 2) increased cyclic AMP production in response to at least one type of neurotransmitter, i.e., to the catecholamine isoproterenol and/or the neuropeptide VIP; 3) on the basis of adenylate cyclase stimulation, beta-adrenoceptors were of the beta 2 subtype and VIP receptors were of a "helodermin-preferring" subtype previously encountered in a human T lymphoblast cell line. Although we analyzed only a limited number of cell lines, it appeared that the immature T BL/VL3 clones responded to peptides of the VIP family with higher potency and efficacy than T helper and T cytotoxic cells. The membranes from the specific TL2-9 helper cell line were without adenylate cyclase activity in the presence of Gpp[NH]p, NaF, and GTP alone or GTP in the presence of isoproterenol or VIP. They produced cyclic AMP in the presence of Mn2+ and forskolin only, suggesting a defect in Gs as in S49 cyc- mouse lymphosarcoma cells. This was further demonstrated by the absence of cholera toxin-stimulated ADP-ribosylation in TL2-9 membranes.