Fluid replacement is a major issue in the treatment of patients with diabetic ketoacidosis. During this therapy, development of pulmonary edema has been reported and attributed to an increase in pulmonary microvascular pressure and a decrease in colloid-osmotic pressure (COP). Because clinically apparent pulmonary edema is associated with an increase in extravascular lung water (EVLW) and impairment of pulmonary gas exchange, we studied the effect of fluid replacement on EVLW, COP, pulmonary hemodynamics and gas exchange parameters in 8 patients with diabetic ketoacidosis (blood glucose greater than 300 mg/dl, pH less than 7.1). EVLW was estimated by the thermal-dye technique. All variables were successively determined upon admission (A), after initial fluid replacement (IFR), when glucose had fallen below 180 mg/dl, after 8 h of intravenous glucose treatment (G), and after 24 h of total parenteral nutrition (TPN). Despite a total net fluid intake of 6.0 +/- 1.61, a significant decrease (p less than 0.001) in COP from 29.6 +/- 5.5 at A to 18.8 +/- 2.2 mmHg after TPE and a significant increase (p less than 0.001) in PCWP from 4 +/- 2 at A to 10 +/- 3 mmHg after TPE, EVLW remained almost unchanged. EVLW was 5.1 +/- 2.8 at A, 5.3 +/- 2.1 after IFR, 4.8 +/- 1.4 after G, and 5.3 +/- 1.7 ml/kg after TPN. However, PaO2 decreased from 137 +/- 17 at A to 87 +/- 10 mmHg after TPE (p less than 0.001), while Qs/Qt increased significantly (p less than 0.05). The alterations in gas exchange may be indicative of pulmonary dysfunction but as they were not associated with accumulation of EVLW, they may as well reflect the compensation of metabolic derangements in diabetic ketoacidosis.