Impaired retention of an inhibitory avoidance response was observed in rats subjected to adrenalectomy (ADX) up to 120 hr before the single learning trial. Corticosterone substitution failed to normalize this behavioral deficit. Rats ADX 240 hr prior to the learning trial showed a normalized behavior. Adrenomedullectomy (ADXM) 48 or 240 hr before learning caused a similar impairment as in short-term ADX rats. The 240-hr ADX rats subjected to corticosterone substitution showed the same behavioral deficit as short-term ADX rats or ADXM ones. Immediate postlearning subcutaneous injection of adrenaline in a dose range of 0.005-5.0 micrograms/kg or of noradrenaline (0.005-0.5 microgram/kg) to 48-hr ADX rats resulted in a dose-related improvement of later retention behavior. Higher doses of catecholamines were less or ineffective. Postlearning treatment of 48-hr ADXM rats with adrenaline (0.5-500 micrograms/kg) caused a similar pattern of behavioral changes. It is concluded that adrenal catecholamines play an important role in the modulation of consolidation of memory. In addition, the high circulating ACTH levels that follow long-term ADX may correct for the behaviorial deficit induced by the absence of adrenomedullary catecholamines.