The aims of this study were: (1) to determine the within-subject, between-day variability in end-tidal PCO2 (PET,CO2); (2) to determine whether the within-subject, between-day variability in PET,CO2 was caused by variations in metabolic acid-base status; and (3) to determine whether between-subject variations in blood gas variables arose predominantly through variations in respiratory or renal pH control mechanisms. Fourteen healthy males were studied, of whom 12 provided adequate data for further analysis. Each subject was studied on at least six different occasions, with each visit separated by at least 1 week. On each occasion, PET,CO2 was determined over a 4-10 min period using a fine nasal catheter taped just inside the nose, and an arterialised capillary blood sample was obtained from each ear and analysed for blood gases. The following results were obtained. (1) PET,CO2 showed a standard deviation (S.D.) for the within-subject, between-day variation of 1.06 mmHg. (2) Less than 5 % (P = NS) of the variability in PET,CO2 could be explained by underlying variations in metabolic acid-base status. (3) The variation in blood gas values between individuals did not fit a pattern associated with either a predominantly respiratory or a predominantly renal origin. Furthermore, the pattern of variation in the blood gas data suggested that variations in the renal controller for pH and the respiratory controller for pH were not independent. The precise origins of variability in blood gas regulation remain obscure. Experimental Physiology (2003) 88.5, 603-610.