Behavioral and biological responses to the muscarinic cholinergic agonist arecoline were studied in bipolar patients and normal twins. Several behavioral response parameters and the prolactin response were concordant in monozygotic twins, suggesting a heritable component. Behavioral, neuroendoncrine, and psychophysiologic responses to arecoline did not distinguish the euthymic patients from controls however. Amphetamine responses in normal volunteers have been further characterized by the use of the blocking agents propranolol, thymoxamine and haloperidol. Data is now being analyzed.