The fetal adrenal cortex has recently been implicated in the etiology of postmaturity on the basis of low cortisol levels found in the plasma of postmature neonates. These findings suggested that labor could be initiated in prolonged pregnancy by iatrogenic elevation of fetal plasma corlisol. In the current investigation designed to test this hypothesis, 500 mg of hydrocortisone sodium succinate, dissolved in the accompanying diluent of bacteriostatic water to form 4 ml of solution, was injected intraamniotically in 10 patients with unfavorable cervices who were 12 or more days past their expected date of confinement. Nine similar patients serving as controls received 4 ml of bacteriostatic water intraamniotically. All patients were followed with daily determinations of urinary estriol. Eight of the 10 patients who received cortisol went into labor within 120 hours of instillation, as compared with 2 of the 9 patients in the control group. Comparison of the two groups revealed a significant difference (p< 0.01). The mean instillation-labor time for the cortisol group was 86 Hours compared with 228 hours in the control group. This difference was also significant (p< 0.001). Urinary estriol excretion declined sequentially following cortisol but not after Infusion of water. These findings are consistent with the hypotheses thata) spontaneous labor in the human may be preceded by a sudden rise in fetal plasma cortisol, as in the sheep;b) the fetal pituitary-hypothalamic axis is responsive to cortisol, hence the falling estriol excretion; andc) ACTH may be the tropic hormone for the provisional zone of the fetal adrenal cortex.