1. Changes in plasma levels of B-END and cortisol were investigated in guinea-pigs receiving either stressful stimuli for various lengths of time or i.p. injections of morphine or saline. 2. A decrease in B-END levels occurred when animals were stressed, whereas cortisol was not affected. 3. Morphine (50 mg/kg i.p.) enhanced B-END and cortisol levels 5 min after injection, whereas a decrease in B-END was seen at 30 min. 4. Saline (i.p.) produced a decrease of B-END levels 30 min after injection and an increase in cortisol 5 and 10 min after injection. These findings suggest that in the guinea-pig the response of pituitary-adrenal axis to stress or morphine could change depending upon the time of sampling.