The possible existence of periods of sensitivity to elevated levels of corticosterone in the postnatal development of the pituitary-adrenal axis was investigated. Long-Evans rats were implanted ip with corticosterone (25 mg/100 g body wt) mixed with an equal amount of cholesterol on postnatal days 3, 6, 12 or 18. Eight blood samples were obtained from each animal at various ages by cardiac puncture. Steroid treatment during the first postnatal week resulted in lowered adult basal levels of plasma corticosterone without affecting the diurnal rhythm. Males treated on day 3 had lowered peak (PM) and trough (AM) levels of the steroid as adults, while males treated on day 6 showed only a lowered PM level. A similar reduction in basal levels of plasma corticosterone was observed in immature females, but did not persist into adulthood. Steroid treatment at day 12 had no effect on basal or diurnal pituitary-adrenal activity. Treatment at day 18 reduced the amplitude of the adult diurnal rhythm in both sexes and delayed the onset of the rhythm in males. No differences in stress responsiveness or adrenal weights were detected. Thus, two distinct periods exist in the postnatal development of the rat during which basal and diurnal pituitary-adrenal activity can be differentially and persistently altered by treatment with the naturally occurring glucocorticoid.