Six male patients with severe ethylene glycol poisoning were studied with respect to the origin of the metabolic acidosis. The plasma concentrations of ethylene glycol were 4-41 mmol/l and treatment included alkali, ethanol and hemodialysis. Plasma analysis by isotachophoresis and whole blood lactate determinations showed that glycolate (17.0-29.3 mmol/l), lactate (1.4-6.2 mmol/l) and beta-hydroxybutyrate (less than or equal to 1.8 mmol/l) were present in elevated concentrations contributing to the acidosis. Oxalate (less than or equal to 0.33 mmol/l), glyoxylate (less than 0.2 mmol/l) and formate (less than 0.4 mmol/l) concentrations were negligible and did not contribute to any significant degree to the acidosis. The elevated plasma glycolate concentration was highly correlated to the anion gap (r = 0.923) and the glycolate made up for 96.1% (n = 6, range 84.7-108.8) of the increased anion gap. We conclude that glycolate accumulation is the main reason for the metabolic acidosis in ethylene glycol poisoning. The mean dialysator (1.6 m2) clearances of glycolate at a blood flow of 200 ml/min in two patients were 137 ml/min (n = 9, SD +/- 8, range 125-149) and 144 ml/min (n = 11, SD +/- 8, range 133-158). By applying first order kinetics during hemodialysis a volume of distribution of glycolate of 0.55 l/kg was found, assuming that the dialysator clearance equals the total body clearance of glycolate. Thus glycolate, the probable main metabolite of ethylene glycol, is efficiently removed by hemodialysis.