The diverse actions of angiotensin II (AngII) are mediated by cell surface receptors. Molecular cloning techniques have identified two distinct subtypes of AngII receptors referred to as AT1 and AT2. It is now well accepted that multiple forms of the AT1 receptor exist, but similar diversity of the AT2 subtype has not been conclusively demonstrated. Nonetheless, several converging lines of evidence do suggest that multiple AT2 receptors may be present in brain and cultured neuron-like cells lines. For instance, some AT2 receptors are regulated by guanine nucleotides and sulfhydryl-reducing agents, whereas others are insensitive. AT2 receptor populations also exhibit differing pharmacological profiles particularly with respect to their affinity for peptidic and non-peptidic ligands. Moreover, a recently developed anti-AT2 polyclonal antisera reveals a unique pattern of immunohistochemical staining in brain and it does not immunoreact with the recently cloned AT2 receptor. Collectively, these results support the hypothesis of multiple AT2 receptors at least within the CNS. Future studies should reveal whether these putative AT2 receptor subtypes result from unique genes or cell-specific post-translational modifications of a single gene product.