We studied the effect of low concentrations (2 to 4%) of inspired CO2 on gas exchange and ventilation-perfusion (VA/Q) relationships in healthy normocapnic anesthetized dogs during constant mechanical ventilation by the multiple inert gas elimination technique (MIGET). One group was studied at normal tidal volumes (12 to 14 ml/kg) and rates (13 to 15/min) in normoxia, and the other in mild hyperoxia (FIO2 = 0.50) and hypoxia (FIO2 = 0.15). In normoxic dogs there were progressive increases in arterial PO2 and reductions in the alveolar-to-arterial PO2 and arterial-to-mixed expired PCO2 differences in response to increases in FICO2. This increased gas exchange efficiency was characterized by reductions in both dead space ventilation and VA/Q mismatch. Better VA/Q matching was characterized by reduction in the log standard deviation of ventilation (log SDV) without significant change in the log standard deviation of perfusion (log SDQ). Gas exchange parameters returned to baseline when dogs were returned to CO2-free inspired gas. In the second group, the effects of 3% inspired CO2 were of comparable magnitude in both mild hypoxia and hyperoxia. In this group (taking hyperoxic values as baseline), there were improved gas exchange and less VA/Q heterogeneity with inspired hypoxia, both with and without inspired CO2. In contrast to the effects of added inspired CO2, improved VA/Q matching with hypoxia was characterized by reductions in both log SDV and log SDQ.(ABSTRACT TRUNCATED AT 250 WORDS)