In 40 patients with cirrhosis on a dietary protein regimen of 1 g/kg b.w., we determined the effect on chronic hepatic encephalopathy of long-term administration of Enterococcus faecium (SF68) versus lactulose. The patients received one of the two treatments for three periods of 4 weeks, each separated by drug-free 2-week intervals. The efficacy of treatment was assessed by arterial blood ammonia concentration, mental status, number connection (Reitan's part A) test and flash-evoked visual potentials. At the end of the third period the reduction in both blood ammonia concentrations and Reitan's test times was more enhanced in patients on SF68 than in patients on lactulose. Furthermore, while patients on lactulose tended to return to basal values during drug-free intervals, responders in the SF68 group maintained improvement throughout the study. In conclusion, SF68 is at least as useful as lactulose for the chronic treatment of chronic hepatic encephalopathy; it has no adverse effects, and treatment can be interrupted for 2 weeks without losing the beneficial effects.