Corticotropin-releasing hormone was discovered in the placenta, and its concentration in the maternal plasma was found to increase greatly during the latter half of pregnancy. We studied the concentration of immunoreactive corticotropin-releasing hormone in amniotic fluid in 59 uncomplicated and in 73 complicated pregnancies. The mean (+/- SE) value of corticotropin-releasing hormone in amniotic fluid in uncomplicated pregnancies was significantly higher in the third (24.1 +/- 3.3 pmol/L) than in the second (9.1 +/- 0.7 pmol/L) trimester, but no change was found during labor. In groups matched by gestational age, larger mean values of corticotropin-releasing hormone and cortisol were observed in the group in which the lecithin/sphingomyelin ratio was greater than 2 or the phosphatidylglycerol test was positive than in the group with a lecithin/sphingomyelin ratio less than 2 or a negative phosphatidylglycerol test result. In samples taken at an interval of 1 to 3 weeks, concomitant increases in corticotropin-releasing hormone and cortisol levels were found with the appearance of phosphatidylglycerol. Concentrations of corticotropin-releasing hormone in amniotic fluid were elevated in patients with diabetes and in women with preeclampsia and intrauterine growth retardation. We conclude that the intrauterine release of corticotropin-releasing hormone increases during the last trimester. This may stimulate the fetal pituitary-adrenal axis and promote fetal maturation.