Plasma ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, subjected to treatment with either a median eminence extract with corticotropin releasing factor (CRF) activity or to ether exposure. 'CRF' injection elevated plasma ACTH levels on all days tested. Ether exposure elevated ACTH levels on days 14 and 21, but not on days 1 or 7. These results indicate: (1) that there is no diminution of responsiveness of the pituitary to direct stimulation by CRF as a function of age, and (2) that the mediators of the stress response above the level of the pituitary are not functionally mature until approximately day 14. Correlations with previous studies also indicate that there is a delay in the return of adrenal responsiveness until some time after these mediators attain maturity.