We compared the performance of a heparinized hollow fiber artificial lung (Medtronic, Minimax) featuring standard hollow fibers (Group A) and experimental hollow fibers with a smaller pore size (Group B). Four sheep in each group underwent a veno-venous bypass for 72 hours. Every 6 hours, at 3 different blood flow rates (BFr) (400, 800, 1200 ml/min), at a constant gas flow rate (Gfr = 4 L/min), and at a constant blood inlet PCO2 (45-55 mmHg), we measured the oxygenation performance (O2 transfer = VO2 and blood outlet PO2 = PO2out), CO2 removal (CO2 transfer = VCO2 and PCO2 outlet = PCO2out) and pressure drop across the device (delta P). A total of about 50 measurement sets were obtained for each group at different time points and blood flow rates. Both groups showed a good oxygenation performance (PO2out always higher than 200 mmHg) and no differences were observed between the two groups (at 1200 ml/min BFr, the average VO2 of all time points was 47 +/- 15 ml/min in group A and 44 +/- 11 ml/min in group B, mean +/- SD, NS). During the first 24 hours, the VCO2 was higher in Group B than in Group A at each BFr (at 1200 ml/min BFr, 81 +/- 18 vs 67 +/- 20 ml/min, p < 0.01), while no differences were observed during the subsequent 48 hours. Throughout the entire experiment, VCO2 increased with increasing BFr in both groups, (in group B, from 43 +/- 14 ml/min at 400 ml/min BFr, to 73 +/- 17 ml/min at 1200 ml/min BFr, average of all time points, p < 0.01). In both groups the delta P increased with the increasing BFr, but it was lower in Group B than in Group A at BFr 800 and 1200 ml/min (at 1200 ml/min BFr, 51 +/- 15 mmHg vs 65 +/- 17 mmHg, p < 0.01), and remained stable for the entire experimental period.