Blood returning from a dialyzer during hemodialysis has a higher pO2 and pCO2 content than blood entering the dialyzer, and this has been attributed to the dialysate. The present study investigates this phenomenon. Acid-base and blood-gas parameters (pH, pO2, pCO2 and HCO3) were measured in three groups of stable chronic hemodialysis patients (A, B, and C) undergoing high-flux hemodialysis. In group A (n = 15), "arterial" (a) and "venous" (v) samples were withdrawn simultaneously before dialysis (samples A0), 5 min after circulation of the blood with the dialysate in the by-pass mode (samples A5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples A10). In group B (n = 11) (a) and (v) samples were withdrawn simultaneously before dialysis (samples B0), 5 min after isolated-ultrafiltration with closed dialysate ports ("isolated-closed" ultrafiltration) (samples B5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples B10). In group C (n = 14), after an initial arterial blood sample withdrawal before hemodialysis (sample C0), high-flux hemodialysis at a zero ultrafiltration rate was initiated. Five minutes later, blood and dialysate samples were withdrawn simultaneously from the hemodialysis lines (samples C5). In all cases blood and dialysate (bicarbonate) flow rates were set at 0.300 and 0.700 L/min, respectively. FLX-18 hemodialyzers (membrane PEPA 1.8 m2) were used in this study. Analysis of variance revealed significant changes only in venous samples. A comparison of arterial and venous samples revealed no differences between groups A and B before the initiation of dialysis (A0a vs. A0v and B0a vs. B0v, P = NS). The pO2 content was higher in A5v samples than in A5a samples (83.5 +/- 11.2 vs. 88.8 +/- 14.0 mm Hg, P < 0.02), while the level of HCO(3) was higher in A5a samples than in A5v samples (20.8 +/- 2.0 vs. 20.4 +/- 1.8 mEq/L, P < 0.05). A10a samples possessed a higher pH and lower levels of pO2, pCO2, and HCO3 in comparison to A10v samples (P < 0.001 for all). Mean pO2 and pCO2 values in A5v and A10v samples increased by 6.3% and 12.1% and by 1.29% and 52% in comparison to corresponding values of A5a and A10a samples, respectively. The pO2 level was the only parameter that differed significantly between B5a and B5v samples (B5a = 84.6 +/- 10.1 vs. B5v = 98.0 +/- 12.6 mm Hg, P < 0.005). B10a samples possessed a higher pH and lower levels of pCO2, pO2, and HCO3 in comparison to B10v samples (P < 0.0005 for all comparisons). Mean pO2 and pCO2 values in B5v and B10v samples increased by 16.2% and 16.3% and by -0.29% and 64.8% in comparison to corresponding values of B5a and B10a samples, respectively. C5a samples possessed a higher pH and lower levels of pCO2, pO2, and HCO3 in comparison to C5v samples (P < 0.001 for all). Mean pO2 and pCO2 values in C5v samples were, respectively, 16.0% and 65.0% higher than corresponding values of C5a samples. These results indicate that blood returning from the dialyzer after 5 min of high-flux hemodialysis has a higher pO2 and pCO2 than blood entering the dialyzer, and that this difference is due to O2 and CO2 transfer from the dialysate space into the blood.