The glucagon-sensitive adenylate cyclase system, viewed from the perspective of its behavior with isolated membrane preparations, displays far more complex regulatory characteristics than could have been envisioned from its behavior in the intact cell. What has emerged from our studies with isolated hepatic membranes is that glucagon can exert at least three actions which we believe are interdependent: desentization of the receptor, activation of adenylate cyclase, and promotion of adenosine inhibition of adenylate cyclase activity. Although the molecular basis remains unknown, GTP is intimately involved in the three processes. Undoubtedly, further levels of complexity will develop when the enzyme system is dissected and its components become amenable to study at the molecular level. At the moment, it is clear that adenylate cyclase systems are provided with a plethora of regulatory processes for controlling cyclic AMP production both in the absence and presence of hormones.