Methods are described for the detection and estimation of guanidinoxy compounds, including canavanine, in biological material. Canavanine has been isolated from the seeds of the bladder senna, Colutea arborescens. A guanidinoxy compound, similar in its colour reactions to canavanine, has been detected in the seeds of Medicago arborea, M. echinus, and Ornithopus perpusillus. Observations have been made from time to time on the effect of previous diet upon carbohydrate metabolism in animals. Samuels, Gilmore & Reinecke (1948) found that, after short periods of fasting, rats on a high-fat diet had lower blood-sugar levels than those on a high-carbohydrate diet. A reduced tolerance in man to orally or intravenously administered glucose (Sweeney, 1927; Himsworth, 1933) and depressed glucose utilization by isolated rat diaphragm (Lundbaek & Stevenson, 1948; Gilmore & Samuels, 1949; Hansen, Rutter & Samuels, 1951) has also been observed as a result of feeding a diet high in fat and low in carbohydrate. In these respects, fat-fed non-ruminant animals show a striking resemblance to the adult ruminant (Reid, 1950a, b; 1952). The purpose of the present work was to confirm these findings in rats and hamsters with a view to reproducing the conditions obtaining in the adult ruminant in non-ruminant animals by suitable modification of the diet. The effect of feeding various diets upon the fasting blood-sugar level, upon glucose tolerance, and upon glucose utilization and glycogen deposition in isolated diaphragm has therefore been examined. Studies on the hexokinase activity of various tissues were included in the hope that they would throw light upon the mechanisms involved.