Angiotensin II receptors are diverse and mediate complex signaling mechanisms. Their isoforms AT₁ and AT₂ have been cloned. AT₁ consists of two closely related subtypes, AT_1A and AT_1B, in rodents. AT_1A is expressed preferentially in the kidney, liver and cardiovascular tissues, whereas, AT_1B is found mainly in endocrine tissues like the adrenal and pituitary glands. In higher mammals only a single isoform of AT₁ has been reported. AT₁ accounts for the majority of actions traditionally ascribed to angiotensin II that include the Gq-protein coupled activation of phospholipase C, Gi-coupled opening of an L-type calcium channel. AT₂ was cloned recently from rat tissues and cell lines. It has a structure compatible with a seven transmembrane domain receptor in spite of the lack of internalization or shift to the low affinity state by stable GTP analogs. AT₂ was found to inhibit certain phosphotyrosine phosphatase(s) by a pertussis toxin-sensitive mechanism. These cloned cDNAs and their mutated cDNAs have been expressed in mammalian cells to identify various functional domains such as ligand binding sites, domains for interaction with various G-proteins, and for desensitization. Both AT₁ and AT₂ genes consist of 3-5 exons. Their coding regions are contained in a single exon. Angiotensin II down-regulates the expression of the AT₁ gene by two different mechanisms, whereas, glucocorticoids up-regulates it. (Hypertens Res 1994; 17:87-97)