1. Modifications by stress of the effects of morphine on pituitary-adrenocortical activity were examined in the guinea-pig at different lengths of time. 2. An increase in plasma cortisol but not in beta-endorphin levels was obtained in guinea-pigs stressed for 60 min. 3. Morphine (50 mg kg i.p.) enhanced beta-endorphin and cortisol levels 5 min after injection and decreased beta-endorphin concentration 30 and 90 min after its administration. 4. In stressed guinea-pigs plasma beta-endorphin levels were reduced 5 min after morphine injection. 5. These results indicate that stress can alter the effects of morphine on pituitary-adrenal activity in the guinea-pig and that the type of modification may be dependent on the time of the sampling.