Urinary free cortisol and progesterone were determined by radioimmunoassay in 18 normal and 16 anencephalic pregnancies and urinary free cortisol levels in 9 nonpregnant women. In normal pregnancy the urinary free cortisol (46.89 +/- 34.02 mug per 24 hours) was significantly higher (P less than 0.001) than that found with anencephaly (17.19 +/- 13.20 mug per 24 hours) and 2 1/2 times (P less than 0.001) the nonpregnant value (18.47 +/- 5.44 mug per 24 hours). In 12 of the anencephalic pregnancies, urinary free cortisol levels (11.05 +/- 5.56 mug per 24 hours) were significantly lower than in nonpregnant women (P less than 0.001). Urinary progesterone levels in normal pregnancy (15.57 +/- 9.66 mug per 24 hours) and anencephaly (18.54 +/- 12.69 mug per 24 hours) were comparable. The cortisol excretion values associated with anencephaly indicate that the normal fetus contributes substantially to the maternal plasma cortisol pool. Urinary free cortisol determinations may be a useful index of fetal adrenal dysfunction.