In previous studies with cirrhotic subjects administration of oral lactulose caused a reduction in the urea production rate associated with an increase in fecal nitrogen excretion. The change in urea production rate in response to lactulose therapy was an indirect measure of a reduction in total gut ammonia production. In this study, the effect of magnesium sulfate administration was compared with lactulose therapy in 5 cirrhotic subjects to determine whether the effects of lactulose on nitrogen metabolism might be attributed to a nonspecific, cathartic effect. Both magnesium sulfate (5-15 g/day) and lactulose (40-80 g/day) caused significant and comparable increases in stool weight, solids, and total nitrogen. Only lactulose caused a reduction in fecal pH. Magnesium sulfate had no significant effect on the urea production rate or urinary nitrogen excretion, whereas lactulose caused a 25% reduction in the urea production rate and an 18% reduction in urinary nitrogen excretion. The latter was accounted for by a fall in urinary urea. Nitrogen balance was more negative during magnesium sulfate than during control or lactulose periods since magnesium sulfate increased fecal nitrogen without altering urinary nitrogen excretion. These data demonstrated that the effects of lactulose on nitrogen excretion and urea metabolism were not duplicated by equivalent cathartic doses of magnesium sulfate.