Alpha- (phentolamine) and beta-adrenergic blocking agents (propranolol) and quinidine similarly enhance the specific binding of TSH to the guinea pig fat cell membranes over the concentration range of 2 X 10(-4) to 4 X 10(-3) M, increasing the binding affinity of TSH to the membranes. The percentage bound increased from 8% in the absence of agents to 32% (phentolamine), 29% (propranolol) and 24% (quinidine), respectively in the presence of these agents (1.5 X 10(-3) M). Each minimal detectable quantity of TSH was approximately 10 microU per tube in the presence of these agents (10(-3) M) as compared to 100 microU per tube in their absence. Both phentolamine and propranolol appeared to enhance the TSH binding to fat cell membranes through membrane-active, non-specific effects besides their alpha- and beta-adrenergic blocking activities.