Muscular subaortic stenosis (MSS) is a genetically determined cardiomyopathy, whereas right ventricular infundibular hypertrophy (IH) apparently is an acquired condition. Since genetic expression in eukaryotic cells may be regulated primarily by DNA-associated proteins, we isolated and characterized the proteins of heart nuclei from nine patients with MSS, eight with IH, and two with normal (N) hearts. More than 150 proteins could be identified by two-dimensional polyacrylamide gel electrophoresis. Proteins in the entire region from pH 7.0 to 9.0 with molecular weights (Mr) ranging from 35,000 to 41,000 and a protein focusing from pH 5.2 to 5.3 with Mrof 55,000 were strikingly reduced in MSS. Again the electrophoretic patterns of N and IH were similar. The electrophoretic patterns of nonhistone nuclear protein (NHNP) in MSS relative to N showed a striking resemblance to those demonstrated previously for the early stage (myolytic phase) of hamster cardiomyopathy relative to the matched control. Since NHNP interacting with DNA appears to play a major role in genetic expression, it is possible that some of the manifestations of MSS could be due to different components of NHNP in the affected hearts.Circ Res 46: 513-519, 1980