Abstract We investigated the influence of the thyroid hormone status on the levels of protein kinase C (PKC) and A (PKA) in the soluble fraction of rat liver. The immunodetectable PKC level in hypothyroid liver was elevated 7.7-fold, whereas the phorbol-ester binding capacity and the immunodetectable α-PKC level were increased 2.4- and 2.6-fold, respectively. Conversely, in hypothyroid livers the abundance of the regulatory type I and the catalytic subunits of PKA were lowered to 42% of the euthyroid level as determined by immonoblotting and by measuring the substrate specific phosphorylation rate of PKA. These changes in the PKC and PKA levels were reversible upon treatment with 0.5 μg T 4/100 g body weight for 2–21 days. The thyroid state dependent alterations in hepatic PKC and PKA levels may be responsible for the Known changes in the response of hepatocytes to other hormonal stimuli in hypothyroidism.