An attempt was made to alter the pituitary-adrenal response to stressful procedures by depleting the brain of norepinephrine and dopamine. This was accomplished by administering reserpine, which depletes 'reserve stores' of catecholamines, and a-mcthyltyrosine (αMT), which blocks catecholamine synthesis, to male rats. Studies on the time course of the actions of both drugs indicated that 24 h after reserpine (2 mg/kg) and 4 h after αMT (50 mg/kg) the brain contents of norepinephrine and dopamine were markedly reduced, while the plasma corticostcrone levels were not significantly different from preinjection control values. At this time animals were subjected to a variety of stressful procedures (administration of ether, histamine or formalin; restraint or altered environment). All stressful procedures increased plasma corticostcrone levels; there was no difference between control and drug-prctrcatcd animals. The concentration of corti- costcrone increased in the plasma of animals tested in motor activity cages. Reserpine and αMT depressed spontanous locomotor activity concurrently with the depletion of brain catecholamines; the drug pretreatments did not alter plasma corticostcrone levels in these same animals. The results suggest that brain catecholamines do not play an essential role in stress-induced activation of the pituitary-adrenal system. © 1968 S. Karger AG, Basel.