To study the effect of antenatal indomethacin or nylidrin hydrochloride treatment on the fetal and neonatal ductus arteriosus and tricuspid valve function, 84 pregnant women with threatened premature birth between 22.9 and 34.0 wk gestation and 94 of their offspring born at 24.7 to 41.6 wk of gestation were studied by Doppler echocardiography. Forty-six women were treated with indomethacin and 38 with nylidrin. Both peak systolic and peak diastolic velocities in the ductus increased after administration of indomethacin and exceeded the corresponding velocities in the fetuses of the nylidrin group (p= 0.0001). Ductal constriction occurred in 42 of 49 fetuses treated with indomethacin (86%). Tricuspid valve regur-gitation (TR) was evident in 11 of 49 fetuses treated with indomethacin (22%). The mean gestational age of the fetuses with TR (30.0 wk) tended to be higher than those without TR (28.3 wk, p= 0.056). In the nylidrin group, no fetus had ductal constriction or TR. A significant increase in peak systolic velocity (r= 0.54, p= 0.0001) and in peak diastolic velocity (r= 0.46, p= 0.0001) in the ductus with advancing gestational age was demonstrated in the indomethacin group; however, in the nylidrin group, there was a less remarkable increase in peak systolic velocity (r= 0.35, p= 0.04) and no increase in peak diastolic velocity (r= 0.02, p= 0.93). In infants born at or before 35 wk gestation, incidences of both spontaneous closure and in-domethacin-induced closure of ductus were similar in both study groups (p> 0.1). Ductal reopening tended to occur more frequently after indomethacin (17%) than after nylidrin (0%) administration (p= 0.15). These findings indicate that: 1) the fetal ductus becomes more reactive to indomethacin with increasing gestational age; 2) TR tends to occur in fetuses with advanced gestational age; and 3) prenatal exposure of indomethacin does not decrease the need for patent ductus arteriosus treatment in premature infants.