Studies on three models of cardiac hypertrophy (aortic constriction, application of isoproterenol, daily administrations of 3,3'5-triiodo-L-thyronine, respectively) reveal that the enhancement of de novo synthesis of adenine nucleotides occurs very early during the development of cardiac hypertorphy and always precedes the increase of protein synthesis. Therefore, it seems likely that the accelerated synthesis of adenine nucleotides is an important factor among those metabolic processes involved in the stimulation of protein synthesis in the hypertrophying heart. 2. As far as the mechanism for the observed enhancement of adenine nucleotide synthesis is concerned, it has been demonstrated that the available pool of 5-phosphoribosyl-l-pyrophosphate, an essential precursor substance of de novo synthesis, is increased in the hypertrophying heart due to isoproterenol and 3,3'5-triiodo-L-thyronine, respectively.