A rapid increase of predominantly unconjugated bilirubin in the blood -- which was not due to haemolysis -- was observed in 38 of 60 patients who had taken an overdose of paracetamol. Studies in the rat given an overdose of the drug showed that within 24 hours there was a striking reduction in the activity of bilirubin glucuronyl-transferase and the content of cytochrome P.450 in the liver. It is suggested that such early damage of the hepatic endoplasmic reticulum contributes to the hyperbilirubinaemia of paracetamol poisoning.