Excessive stretch of heart muscle is thought to be a determinant of myocardial hypertrophy. Because cell shape and nuclear shape are closely coupled in cardiac myocytes, we hypothesize that excessive stretch causes physical deformation of the nucleus which might be responsible for some molecular events leading to hypertrophy. Cell shape and nuclear shape are most likely to be coupled by cytoskeletal elements. With this in mind, we have used immunogold labeling to examine the topological associations of desmin cytoskeletal and lamin B nucleoskeletal intermediate filaments with various intracellular structures in mammalian cardiac myocytes. We found that desmin filaments form a sarcoplasmic network radiating from the sarcolemma to the nuclear surface. Perpendicular to the long axis of the cell, strands of desmin filaments traverse the interfibrillary space in a co-linear arrangement with Z-discs. The desmin filament strands extend between peripheral regions of adjacent Z-discs. Desmin filaments traversing the interfibrillary space closely associate with the surface of mitochondria. At the cell surface, desmin filaments extend from Z-discs to terminate immediately beneath the sarcolemma. Close to the nucleus, desmin filaments extend from Z-discs towards nuclear pores. At the same time, lamin B filaments, which co-localize with heterochromatin immediately beneath the inner nuclear membrane, encircle the inner aspects of each nuclear pore. We hypothesize that desmin and lamin B are functionally anchored to each other at the nuclear pore, either directly or through anchorage proteins within the pore complex. This transcellular intermediate filament network would serve to physically couple the shape of the cell to that of the nucleus, where shape changes might have molecular consequences responsible for development of myocardial hypertrophy.