Studies using various labeled substrates are being performed to learn more about the metabolic effects of clofibrate on the ciliated protozoan Tetrahymena pyriformis, with a view towards quantitating the changes in flux along the major pathways of intermediate metabolism caused by this drug. Measurements of label incorporation from acetate, pyruvate, glucose, ribose, leucine, and H14CO3 into CO2, glycogen, and the glycerol and fatty acid moieties of the lipids will be made and interpreted with the aid of a comprehensive model of intermediary metabolism of this cell. Studies have also been initiated with the long term goal of developing a quantitative model of intermediary metabolism in isolated rat hepatocytes. At present we are studying the effects of glucagon and angiotensin on the metabolism of fructose and mannose by hepatocytes, in an attempt to determine whether there are multiple pools of glucose-6-phosphate in this cell.