The effects of the central and peripheral administration of atriopeptin II, a 23-amino acid residue peptide of atrial natriuretic peptide (Ser103-Arg125) on anxiety-related behavior and on locomotor activity, was studied in male Wistar rats. Their behavior on the elevated plus-maze after social defeat stress indicated that intracerebroventricular (2.5 and 5 micrograms) and intraperitoneal (50 micrograms) administration of atriopeptin II produced anxiolysis. A low dose of 0.25 micrograms atriopeptin II administered bilaterally into the central nucleus of the amygdala was also found to be anxiolytic. Because intracerebroventricular administration of 5 micrograms atriopeptin II did not affect locomotor activity in the open-field test, the possibility that the anxiolytic effect was secondary to sedation could be ruled out. The anxiolytic effects observed after central and peripheral administration support the idea that atrial natriuretic peptide, which is increased in panic-anxiety, may be involved in the tapering of anxiety-related behavior.