Utilizing biologically active 125I-labeled gonadotropin-releasing hormone (125I-GnRH), specific binding with two affinites [KA (high) = 3.2 x 10(8) M-1, KA (low) = 10(5) M-1] were identified in membrane preparations derived from the 10,800 x g pellet of rat pituitary. GnRH-specific low affinity sites (KA - 10(5) M-1) were identified in liver, spleen, renal cortex, lung, testis, ovary, and cardiac muscle. Hypothalamic tissue demonstrated both high- and low-affinity binding. When 125I-GnRH was bound and dissociated, the labeled GnRH retained fully ability to rebind to fresh membrane preparations. That is, binding was not associated with loss of biological activity of GnRH. However, when unbound 125I-GnRH was exposed to the membrane fraction of liver, almost all receptor binding activity disappeared. The presence of low-affinity binding sites in peripheral tissues raises several possibilities: 1) they act as a simple reservoir mediating metabolic clearance of GnRH; 2) they represent enzyme binding sites involved in degradation of GnRH; 3) they mediate peripheral actions of GnRH; or 4) they are simply a cellular membrane constituent unrelated to target actions of GnRH.