Circulating glucocorticoids play a role during the immediate postnatal period in adapting the neonate to extrauterine life and are also thought to influence tissue development and function in the later postnatal period. In the present study we have used a rat model to test whether birth by cesarean section (C-section), either alone or with an added period of acute anoxia, affects the developmental profile of basal corticosterone secretion during the first 5 wk of life. Plasma levels of total corticosterone and of corticosteroid-binding globulin were measured at various times after birth in rats born vaginally, by C-section, or by C-section with 15 min of added anoxia. These measures allowed for calculation of levels of free, biologically active, corticosterone. Under all conditions, total corticosterone appeared to accurately reflect levels of free corticosterone. Plasma corticosterone levels measured immediately (<5 min) after birth were similar in male rat pups born vaginally, by C-section, or by C-section with added anoxia, whereas female pups born by C-section showed a significant increase in free corticosterone at birth, in comparison with vaginally born females. Both male and female animals born by C-section showed a reduction in plasma corticosterone at 1 h (male: 31% of control,p< 0.01; female: 45% of control,p< 0.05) and at 7 d (male: 61% of control,p< 0.01; female: 55% of control,p< 0.05) after birth, in comparison with vaginally born controls. In animals born by C-section with added anoxia, significant reductions in plasma corticosterone were observed for males at 1 h (58% of control;p< 0.05) and for females at 7 d (62% of control;p< 0.05) after birth. At 14 d of age, corticosterone levels were higher in male rats born by C-section either with (227% of control;p< 0.05) or without (239% of control;p< 0.05) added anoxia, in comparison with vaginally born controls. Thus C-section birth produces an early rise in plasma corticosterone on d 14 away from the low values associated with the adrenal quiescent period in the first 1-2 wk in the rat. By 35 d of age, there were no differences in plasma corticosterone attributable to C-section birth and/or acute birth anoxia, in either male or female rats. It is concluded that, in a rat model, birth by C-section has significant effects on the profile of plasma corticosterone during the early weeks of development, a period thought to be critical for effects of corticosteroids on developing tissues. Because the rat at birth is developmentally less mature than is the term human neonate, these findings may have implications for development of the premature human neonate.Abbreviations: C-section,cesarean section;GC,glucocorticoid;CBG,corticosteroid-binding globulin