Digestion of pituitary membranes with phospholipase A 2 and phospholipase C abolished, in a dose responsive manner, the specific binding of gonadotropin releasing hormone agonist and antagonist. These reductions in gonadotropin releasing hormone binding capacity stem from a decrease in the affinity of both agonist and antagonist. Digestion with phospholipase A 2 was calcium-dependent, whereas digestion with phospholipase C was calcium-independent. Treatment of the membranes with phospholipase D reduced the binding to a smaller degree but affected more significantly the binding of the agonist than that of the antagonist. These data show that membrane phospholipids are involved in the gonadotropin releasing hormone-receptor interaction.