To determine the effect of humoral factors and their interaction on the development of acute hypoxic pulmonary pressor response (HPPR), we performed studies in 16 mongrel dogs. We measured plasma levels of noradrenaline (NE), angiotensin II (AII), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6KPGF1 alpha), thromboxane B2 (TXB2), leukotriene B4 (LTB4) and 5-hydroxytryptamine (5-HT) before, during and after HPPR. Multiple regression analysis showed that the changes of pulmonary arterial systolic pressure (PASP) and pulmonary arterial diastolic pressure (PADP) correlated well with those of plasma concentration of NE, PGF2 alpha and 6KPGF1 alpha, respectively (r were equal to 0.633 and 0.668, respectively, P < 0.01). The results of orthogonal experiment analysis with an injection of exogenous NE, PGF2 alpha and PGI alpha into main pulmonary artery of dogs showed that NE and the interaction of PGF2 alpha and PGI2 alpha increased PASP (P < 0.05) and PGI2 attenuated PASP (P < 0.01). The interaction of PGF2 alpha and PGI2 and of PGF2 alpha and NE increased PADP(P < 0.01) and PGI2 attenuated PADP (P < 0.01).