The first adenylate cyclase-linked receptor showing a decreased affinity due to the presence of guanine nucleotides, was the glucagon receptor of rat liver plasma membr~es [ 1). Guanine nucleotidedependent modulation of agonist binding to a /3-adrenergic receptor, was initially shown in plasma membranes from cultured rat glioma cells (C6) [2], and has since been observed in membranes from frog erythrocytes [3f, and other cells [4,5]. Guanine nucleotide modulation has also been found for receptors [6-81, which on interaction with adenylate cyclase results in inhibition. Although, the dependence on guanine nucleotides for /.l receptor-mediated activation of adenylate cyclase [9-l l] in avian erythrocyte membranes is well documented, the bind~g of agonists to the fl receptor has been reported to be unaffected by guanine nucleotides [ 12-141. To explain the absence of guanine nucleotide-mediated receptor modulation, and the lack of agonist-dependent desensitization of adenylate cyclase, it has been proposed that avian erythrocyte membranes may lack an additions GTP binding protein present in other cells [IS]. This study aimed to clarify these controversial points.