Factors which could influence serum erythropoietin (s-EPO) levels in patients with chronic pulmonary diseases were investigated, paying special attention to the role of changes in acid-base balance (PaCO2, HCO3- and base excess levels) in EPO production. Data from 30 patients with chronic pulmonary diseases (chronic pulmonary emphysema, chronic bronchitis and post-tuberculosis status) were obtained in the morning and were analyzed with a stepwise forward multiple regression analysis, evaluating the statistical significance of seven factors which may potentially influence s-EPO levels: arterial pH, PaCO2, PaO2, HCO3-, base excess (BE), SaO2 and hemoglobin (Hb). Significant simple correlations (P < 0.01) of log(s-EPO) were obtained with PaO2 (r = -0.66), PaCO2 (r = 0.59), HCO3- (r = 0.67), BE (r = 0.71) and SaO2 (r = -0.77). The stepwise forward multiple regression analysis revealed that significant correlate variables for the outcome variable of log(s-EPO) were SaO2 and BE, with r = 0.823 (P < 0.0001). In patients with chronic pulmonary diseases it was shown that SaO2 was a negative correlate and BE was a positive correlate of s-EPO levels. It was speculated that s-EPO levels in the morning reflected daytime hypoxemia (SaO2) and nocturnal desaturation evoked by hypopnea during sleep (indicated as BE) in these patients.