A recent report (J. Appl. Physiol. 38: 382-388, 1975) suggests that negative blood-gas CO2 partial pressure (PCO2) differences exist in the dog during hypercapnia, as mean expired PCO2 exceeded arterial PCO2 by more than 10 Torr when the CO2 fraction in inspired gas (FICO2) was 0.1. We have reinvestigated this problem in anesthetized dogs breathing spontaneously room air or hypercapnic mixtures (FICO2 = 0.05 or 0.10). During steady state, arterial blood samples were analyzed with electrodes, care being taken to keep the electrode temperature within +/- 0.2 degrees C at the actual aortic temperature of the animal. Respired gas was measured at the tracheostomy by a sensitive low-noise respiratory mass spectrometer. During room air breathing, the arterial-end-expired PCO2 difference, P(a-E')CO2, averaged +5 Torr and decreased to +0.9 Torr and to +0.1 Torr with FICO2 = 0.05 and 0.1, respectively. Hypoxia (FIO2 = 0.10) had no apparent effect on the P(a-E')CO2 difference. We ascribe the decrease in P(a-E')CO2 with hypercapnia to the diminishing effects of alveolar dead space, whereby end expired PCO2 approached arterial PCO2. We then conclude that in blood-gas equilibration lungs, PCO2 in end-capillary blood comes close to alveolar PCO2, and that the negative blood-gas PCO2 differences reported earlier are probably caused by deficiencies in the techniques used.