The effects of hypoxia on contraction of sheep pulmonary artery rings (large = 2.2-4.1 mm diameter, small = 0.32-0.64 mm diameter) has been investigated following precontraction or with the artery rings set at their optimal resting force. Hypoxia (PO2 4 mmHg) caused a marked contraction of pulmonary artery rings precontracted with 5-HT at its EC85 (small arteries 40 +/- 8 g cm-2) but not when precontracted with KCl. At optimal resting force hypoxia caused a small contraction (small arteries 11 +/- 2 g cm-2). Larger artery rings gave a smaller contraction in response to hypoxia at optimal resting force than did small artery rings (2 +/- 0.2 g cm-2 at PO2 = 4 mmHg). Large, unlike the small, artery rings did not contract in response to hypoxia when precontracted with 5-HT at its EC35. Lowering the PO2 to 40 mmHg caused contraction in arteries precontracted with 5-HT at its EC85 but not in arteries at their optimal resting force. Removal of the endothelium abolished all hypoxia-induced contractile responses in sheep pulmonary artery rings. Hypoxia reversibly abolished acetylcholine-induced relaxation and augmented the 5-HT contraction (206 +/- 28 to 255 +/- 34 g cm-2) in small rings. It is concluded that hypoxia may produce contraction in sheep pulmonary artery rings at least, in part, by reducing the output of vasodilator mediators from the endothelium.