SUMMARY A lack of correlation between blood pressure and myocardial hypertrophy was established in spontaneously hypertensive rats, suggesting that factors other than blood pressure control might be responsible for the modulation of myocardial hypertrophy. An in vitro system that is independent of blood pressure and hemodynamic effects was developed by use of isolated myocytes to study myocardial protein synthesis. The validity of this system was determined by means of morphology, by receptor integrity, and by studying the incorporation of tritiated leucine into myocyte protein (dpm/mg/hr). Addition of a supernatant of spontaneously hypertensive rat myocardial homogenate (centrifuged at 1500 g) to the myocyte system resulted in a significant increase in tritiated leucine incorporation into myocyte protein when compared with the addition of homogenates from normal controls. The protein from the homogenate was partially purified by high performance liquid chromatography. The resultant purified protein also stimulated protein synthesis by 70%. Furthermore, a significant increase in the specific activity of the transfer RNA and the rate of protein synthesis was observed after addition of homogenate from hypertrophied heart (4.02 ± 0.3 vs 7.0 ± 0.2 pmol leucine//xg protein/hr; p< 0.05). These data demonstrate the existence of a soluble factor in the hypertrophied myocardium that stimulated protein synthesis. This factor may play a key role in modulation of myocardial structure during development or regression of myocardial hypertrophy in hypertension. 3 ' 4 We, 2 ' *~7 as well as others, 8 "" have shown that factors other than blood pressure controls are involved in the development or reversal of myocardial hypertrophy in hypertension. Several hypotheses can be advanced to account for the factors) responsible for an increase in muscle mass as a result of increased protein synthesis. The most plausible hypothesis is that the mechanism resides entirely within the cells. When the heart is exposed to stress, there might be local release of a factor that triggers protein synthesis.To examine this hypothesis, it is essential to have an in vitro assay system that is independent of blood pres-