SUMMARY: The activation of adenyl cyclase in intact mouse thyroid glands was measured by the conversion of [3H]ATP to [3H]cyclic AMP. Untreated serum had an inhibitory effect. Human thyroid-stimulating hormone (TSH) and γG-globulin prepared from serum containing the long-acting thyroid stimulator (LATS), activated adenyl cyclase and the log-dose—response relationship did not deviate from parallelism. The rate of activation by LATS was slower and the peak response was delayed, compared with the response to TSH. The possible significance of this is discussed. Other hormones and neurotransmitters examined had no effect on thyroidal adenyl cyclase.