The effect of starvation and of protein-deprivation on the extractable amount of cardiac mRNA was investigated in male rats. Cardiac mRNA was determined by either (a) isolation of cardiac mRNA by SDS-Phenol/oligo-dT-cellulose, or by (b) hybridization of cardiac mRNA to 3H-Poly(U). During starvation (1-6 days) the extractable amount of cardiac microsomal RNA decreased from 870 micrograms/g heart (controls) to 606 micrograms/g (3 days) and to 547 micrograms/g (6 days), the extractable amount of mRNA fell from 28.6 micrograms/g heart (controls) to 18.7 micrograms/g (3 days) and to 14.5 micrograms/g (6 days). When a normocaloric but protein-deficient diet was fed, the decreases in cardiac microsomal RNA and mRNA were qualitatively similar, but slightly less severe. An analysis of the intracellular distribution of cardiac microsomal RNA and mRNA in the hearts of normal animals and of animals starved or fed a protein-deficient diet indicates that during starvation cardiac mRNA does not accumulate in the cell sap, but gets rapidly degraded. In the refeeding period, mRNA is transported from the nucleus to the cytoplasm and engages in polyribosome formation. The specific mRNA species coding for the major myofibrillar cardiac proteins are affected to a similar extent by these changes during starvation/protein-deprivation and refeeding.