To study the factors involved in the anorexia and hyperpyruvicemia of thiamine deficiency, rats were force-fed a liquefied thiamine-deficient diet by stomach tube. Force-feeding decreased the life expectancy of thiamine-deprived and oxythiamine-treated (OTh) rats by 0.33 to 0.50%, compared with similar rats fed ad libitum, but had no effect on life expectancy of pyrithiamine-treated (PTh) rats. Bloating was observed in all force-fed deficient groups and appeared to correlate well with the development of anorexia in rats fed ad libitum. It was so severe in force-fed OTh-treated rats that the daily food ration had to be cut by one-half. Thiamine-deprived and OTh-treated rats still showed significant increases in blood pyruvate and plasma corticosterone levels, and in gut and adrenal weights despite force-feeding to reduce inanition. Longer treatment with OTh appeared to exhaust the ability of the adrenals to put out corticosterone. PTh treatment resulted in increases in plasma corticosterone and adrenal weight in the ataxic but preconvulsive state, which increased further after convulsions had started, along with a significant increase in blood pyruvate. Because the animals are unable to use the food these results suggest that the anorexia is the result of some local biochemical disturbance in the gut, and that elevations of blood pyruvate in thiamine-deficient states are possibly due to two factors: a hyperactivity of the hypophyseal-adrenal system, and specific disturbances in pyruvate metabolism.