The effects of intragastric feeding with glucose and of the administration of L-triiodothyronine (T3) on in vivo rates of hepatic lipogenesis were investigated in control (fed ad libitum on normal diet), diabetic (fed ad libitum on normal diet), fat-fed (fed ad libitum on high-fat diet), and starved (food removed for 48 h) rats. Two days of T3 treatment increased hepatic lipogenesis in control and fat-fed animals but not in the diabetic or starved animals, although increases in lipogenesis in diabetic animals were observed after 4 days of T3 treatment. Intragastric glucose feeding increased hepatic lipogenesis in the livers of control animals and T3-treated control animals. Such increases are mediated by an increase in the circulating insulin concentration, as increases are not observed in diabetic rats or T3-treated diabetic rats. Glucose feeding failed to increase hepatic lipogenesis in fat-fed rats or starved rats. Insulin injection together with glucose feeding increased lipogenesis in the fat-fed group but not the starved group; i.e., impaired insulin secretion following an oral glucose load may in part explain the lack of response in the fat-fed but not the starved animals. Marked increases in hepatic lipogenesis after glucose feeding were, however, observed if either the starved or the fat-fed animals were treated with T3. The physiological implications of these observations are discussed.