It is generally believed that nuclear enlargement indicates polyploidy. The purpose of this study was to establish whether nuclear enlargement is also a marker for cellular hypertrophy. Using isolated myocytes, we examined the growth of cardiac myocyte nuclei during cellular hypertrophy in rats with aortocaval fistulas or left ventricular myocardial infarction. A Coulter Channelyzer was used to measure the volume of the myocytes. Isolated myocytes were stained with the DNA-specific fluorochrome 4'-6-di-amidino-2 phenylindole-HCl for measurements of nuclear length and width, and calculation of nuclear volume. One week, 1 month and 5 months after aortocaval fistula surgery, the nuclear volume of right ventricular myocytes increased by 24, 55 and 56% respectively. Increased length, rather than width, accounted for most of the nuclear growth. Nuclear hypertrophy was associated with a progressive increase in cell volume at each time point (34, 88 and 118%). Adaptive growth of left ventricular myocytes followed the same trend, though the extent of cellular and nuclear hypertrophy was reduced. One month after producing a myocardial infarction, there was an increase in nuclear volume (18%) and nuclear length (11%) in right ventricular myocytes, but no changes in the surviving left ventricular myocytes. The cell volume increased in both right and left ventricles (72 and 18%, respectively). Thus, nuclear size increased as myocytes enlarged, though at a slower rate. Since nuclear DNA content does not increase in rats with aortocaval fistulas or myocardial infarction, the increase in nuclear volume was associated with cellular enlargement rather than increased polyploidy.