Administration of triamcinolone or dexamethasone to rats led to a prompt, marked and persistent rise in liver acetyl‐CoA carboxylase activity. The activity of fatty acid synthetase increased to a lesser extent and after a more prolonged glucocorticoid treatment, whereas the changes in that of NADP‐malate dehydrogenase and ATP‐citrate lyase were not appreciable. The overall channeling of [1‐¹⁴C]acetyl‐CoA to fatty acids was enhanced. The triamcinolone effect on acetyl‐CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan‐diabetic rats, whereas the alanine‐aminotransferase‐inducing effect of this hormone was additive to that of insulin deficiency. In adipose tissue triamcinolone treatment caused a reduction in the activity of all lipogenesis enzymes and blunted their response to insulin administration. The antagonism of glucocorticoids toward insulin, selectively modulating the responses of the insulin‐sensitive enzymes in liver and adipose tissue is discussed. The rise in hepatic lipogenic capacity, through the retention of the ability of insulin to induce acetyl‐CoA carboxylase, may be physiologically important in restraining the ketogenesis from acetyl‐CoA despite the increased fat utilization during glucocorticoid excess.