We performed single-breath tests in closed-chest, paralyzed, and anesthetized dogs (6 with bilateral vagotomy and 6 with intact vagi) with the heart beating and during cardiac arrest. Repeated cardiac arrest was achieved by ventricular fibrillation and subsequent defibrillation. Twenty-four single-breath tests per dog were performed in combinations of three inspiratory volumes (VI; 0.2, 0.5, and 0.8 liter) and four postinspiratory pauses (0, 5, 10, and 30 s), either with or without cardiac arrest. The test gas contained four inert relatively insoluble gases (He, Ne, Ar, and SF6) with a sixfold range in diffusivity. Series dead space (VD) decreased with increasing postinspiratory pause, increasing gas diffusivity, or decreasing VI. In vagotomized animals, VD was smaller with the heart beating than during cardiac arrest, but this relationship was reversed in animals with intact vagi. The decrease in VD due to cardiogenic mixing accounted for only 10.8% of the total decrease in VD occurring during a 30-s postinspiratory pause. The slope of phase III decreased with increasing postinspiratory pause except at VI of 0.2 liter. No significant differences were noted in the slope of phase III between experiments performed with the heart beating or arrested. Tracer gas retained in the residual volume after expiration increased with increasing inspiratory pause. Gas retention was greater for He than for SF6 but was not affected by cardiac action. These findings indicate that cardiac action mainly affects the interface between inspired and alveolar gas and has little effect on mixing in the alveolar compartment.