Three experiments were conducted to investigate interactions between acetate and glucose metabolism in sheep fed on roughage-based diets, and to establish whether the clearance rate of an intravenous acetate load would provide a valid index of the dietary acetate:glucogenic precursors ratio. In Expt 1 lambs were fed on a basal diet of wheat straw and supplemented with propionate and protein. Both supplements increased glucose irreversible loss rate (ILR) although not to the same degree. Acetate clearance rates were increased by protein and propionate supplementation and were positively related to glucose ILR irrespective of precursor. In Expt 2 the effects of an increased dietary load of acetate given with or without propionate were investigated. Glucose ILR did not respond to acetate supplementation, but was increased when propionate was fed in addition to acetate. This was reflected in an unchanged ability to clear an intravenous acetate load from the blood when acetate alone was added, but an increased acetate clearance rate when propionate was fed in addition to acetate. In Expt 3 the effects of supplementation with various propionate: Acetate ratios were investigated. Acetate clearance was consistently increased by an increased propionate: Acetate ratio. These results show that the metabolism of excess acetate is responsive to the dietary supply of glucose precursors, and provide support for the concept that additional glucose precursors are necessary for the efficient utilization of acetate when roughage diets low in protein are fed.