In adult mammals, arterial blood gases closely reflect lung gas composition, and arterial blood gases can, therefore, be effectively regulated through changes in ventilation. This is not the case among most ectothermic vertebrates, where the systemic and pulmonary circulations are not completely separated, resulting in central vascular shunts. In the presence of a right-to-left shunt (R-L shunt), the O2 levels (PO2 and haemoglobin O2-saturation) of systemic arterial blood are depressed relative to those of the blood returning from the lungs. Arterial blood gas composition is, accordingly, not determined only by ventilation, but also by the magnitude of admixture as well as the blood gas composition of systemic venous blood. Changes in the central shunt patterns, therefore, represent an alternative mechanism by which to control arterial blood gas levels. The primary aim of this report is to evaluate the relative importance of the R-L shunt and ventilation in determining arterial blood gas levels. Using standard equations for gas exchange and the two-compartment model, we predicted arterial O2 levels at physiologically relevant levels of ventilation, R-L shunt and blood flows. The analyses show that the effects of changing ventilation and the size of the R-L shunt on arterial O2 levels vary with parameters such as the rate of O2 uptake, the blood O2-carrying capacity and the level of hypoxia. The relative importance of ventilation and the R-L shunt in determining arterial PO2 values is largely explained by the sigmoidal shape of the O2 dissociation curve. Thus, if lung PO2 is high relative to blood O2 affinity, a large change in ventilation may have little effect on pulmonary venous O2 content, although PO2 may have changed considerably. If an R-L shunt is taking place, this, in turn, implies that arterial O2 content is affected only marginally, with a correspondingly small effect on PO2. These predictions are discussed in the light of the limited existing experimental data on cardiac shunts in lower vertebrates; we propose that, in future experiments, the measurement of both ventilatory and cardiovascular parameters must be combined if we aim to understand the regulation of arterial blood gas levels in lower vertebrates.