These studies investigated the activation and inhibition (negative feedback) of the neonatal rat. The ACTH response of maternally deprived pups is persistently elevated for 30 min, suggesting a deficiency in the negative feedback system. In Experiment 1, we examined the time-course of corticosterone (CORT) and ACTH responses to a saline injection over a 120-min period during development. In deprived pups, CORT and ACTH were persistently elevated throughout the testing period, whereas only 15-day-old nondeprived pups showed ACTH and CORT elevations. Further nondeprived and deprived pups were exposed twice to ether (Experiment 2) or saline injections (Experiment 3) separated by a 1-h interval. Nondeprived pups showed an augmented ACTH response to double exposure to ether, but not to saline. No CORT response to either stimulus was observed. In response to one exposure of each stimulus, deprived pups showed increased ACTH and CORT values and no further elevation to repeated exposure. These results suggest the negative feedback system of neonates is immature, but partially functional in deprived pups. Moreover, nondeprived pups show a stressor-specific response to stress, whereas deprived animals show a similar response to different stimuli.