The purpose of this study was to determine the effect of gestational age, labor, and microbial invasion of the amniotic cavity on amniotic fluid concentrations of endothelin-1,2. Amniotic fluid was retrieved by amniocentesis from 148 women: patients at term with and without labor, patients with preterm labor with and without intraamniotic infection, and women in the second trimester of pregnancy. Endothelin-1,2 was measured by a sensitive and specific radioimmunoassay. Immunoreactive endothelin-1,2 was detectable in all samples of human amniotic fluid. Advancing gestational age and spontaneous term labor did not result in changes in amniotic fluid concentrations of endothelin-1,2. Women with preterm labor and positive amniotic fluid cultures for microorganisms had higher amniotic fluid concentrations of endothelin-1,2 than did those without microbial invasion of the amniotic cavity (p less than 0.05). These results support a role for endothelins in the mechanisms responsible for preterm delivery associated with intraamniotic infection.