The O2 tension of umbilical arterial blood in utero is 15 mmHg. The contractile effect of increasing the O2 tension above this value was studied quantitatively in vitro in preparations of human umbilical artery and vein. The umbilical arterial smooth muscle was contracted in a concentration-related manner by stepped increments in O2 tension. The threshold for O2-induced contraction was estimated to be 36 mmHg at pH 7.28 and the maximum contraction occurred at 297 mmHg. The sensitivity of the preparations to low O2 tensions (less than 100 mmHg) was reduced by increasing the pH of the bathing medium from 7.28 to 7.36, at which the threshold was 69 mmHg and the maximum contraction occurred at 282 mmHg. Reducing the pH to 7.18 did not significantly change the sensitivity from that found at pH 7.28. Indomethacin (0.1 microM) virtually abolished responses to O2. The results indicate that the increase in the physiological O2 tension at birth, from 15 to 100 mmHg, may be an adequate stimulus to effect the closure of the umbilical artery. In the physiological range O2 did not contract the umbilical venous smooth muscle. This may allow the transfusion of blood from the placenta to the fetus at birth when the O2 tension of umbilical cord blood increases after the onset of breathing.