Embolic pulmonary hypertension is associated with alterations in gas exchange of variable severity, which we hypothesized to be related to embolus size. We therefore examined the effects of different-size autologous blood clot embolization on pulmonary arterial pressure-cardiac output relationships (Ppa/Q) and on the distribution of ventilation-perfusion ratios (VA/Q) in 18 intact anesthetized and ventilated (inspired fraction of O2 0.4) dogs. Multipoint Ppa/Q plots were generated by a manipulation of venous return before and 60 min after sufficient amounts of small (1 mm, n = 6 dogs), medium (5 mm, n = 6 dogs), or large (10 mm, n = 6 dogs) clots to increase Ppa to 50 mmHg. The distribution of VA/Q was determined by the multiple inert gas elimination technique at the same intermediate Q in each of these experimental conditions. All three sizes of emboli resulted in an 82-92% mean angiographic pulmonary vascular obstruction and increased both the extrapolated pressure intercepts and the slopes of the linear Ppa/Q plots. Gas exchange was altered the most after large clots, which were associated with lower arterial pH, higher physiological and inert gas dead spaces, higher dispersion of ventilation, and also lower mean VA/Q of perfusion distributions. In contrast, inert gas dead space was decreased after small clots. We conclude that, in autologous blood clot embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size but that gas exchange is affected differently, mainly in high-VA/Q regions and most often after the largest clots.