Acute hepatic failure was induced in rats by galactosamine injection intraperitoneally (1 gm per kg). Twenty-four hours later rats were treated by hemoperfusion (HP) over encapsulated sorbents: cellulose acetate-coated charcoal, polyelectrolyte-coated XAD4, a combination of both, or cross circulation with a healthy donor. Compared with control treatment (prevention of hypoglycemia by glucose infusion), the survival rate was not improved by HP or cross circulation: controls 19% vs. treated animals 0 to 17%. Extension of duration or increased frequency of HP gave the same survival rates. Computer simulation based on zero-order introduction of a possible toxin into a two-compartment model shows that HP up to 5 hr per day is not able to clear the body effectively from the assumed toxin if its partition coefficient exceeds a value of 50.