Known synergism between forskolin and hormones in adenylate cyclase activation leads to the supposition that hormone might stimulate forskolin binding. That possibility was tested using intact wild type S49 cultured lymphoma cells. Using 40 nM [3H]-forskolin it was shown that the extent of forskolin binding using a filtration technique increased with the concentration of epinephrine or isoproterenol (INE). Moreover, the hormone-dependent forskolin binding was stereospecific (requiring l- rather than d-epinephrine), it was not observed in the cyc- variant and it was not inhibited by cytochalasin B. These observations lead to the conclusion that the binding is specifically associated with the adenylate cyclase system and requires a functional Gs unit. Epinephrine-stimulated forskolin binding did not correlate exactly with forskolin activation of adenylate cyclase in the presence of similar concentrations of epinephrine. It was concluded from that observation that there is not a one to one correspondence between binding and activation.