Patients with end-stage renal disease treated by hemodialysis with bioincompatible membranes are exposed during the dialysis period to acute effects on lung microcirculation, which may result in pulmonary fibrosis and diffusion defects in long-standing dialysis. To investigate the occurrence of these possible chronic pulmonary alterations, we determined lung function in patients with chronic renal failure not undergoing hemodialysis and in patients who had been receiving regular hemodialysis both for short and long periods of time. Forty-three patients divided into three groups were studied: 17 patients before dialysis with a mean (SD) creatinine clearance of 14.1 (6.8) ml/minl 1.73 m², 10 patients receiving regular hemodialysis for a period of less than 12 months (mean 6.4 ± 3.5 months), and 16 patients receiving regular hemodialysis for more than 5 years (mean 8.3 ± 3.6 years). First-use bioincompatible cellulosic dialysis membranes were used in all the cases. The following parameters were recorded: forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), total lung capacity (TLC), residual volume (RV), carbon monoxide transfer factor (T_LCO), accesible lung volume (V_A), carbon monoxide transfer factor/accesible lung volume (K_CO— that is, T_LCO/V_A), and arterial blood gases. Patients receiving regular hemodialysis for more than 5 years showed significantly lower values of T_LCO and K_CO than patients before dialysis and patients receiving regular hemodialysis for less than 12 months. Seventy-five percent of patients on long-term hemodialysis had markedly reduced T_LCO or K_CO values (below 80% of the reference value) as compared with 17% of patients before dialysis and 10% of patients dialyzed for less than 12 months (P<0.001). Differences among groups for the remaining parameters were not observed. In conclusion, patients undergoing long-term regular hemodialysis with a bioincompatible membrane showed a selective reduction in pulmonary diffusing capacity possibly due to chronic pulmonary fibrosis.