Endothelial cell transplantation onto polymeric vascular grafts results in the formation of a neointima, The formation of this neointima is often suggested to result from a chronic cellular hyperplasia where the terms intimal hyperplasia and intimal thickening are used interchangeably. While the formation of a midgraft neointima in sodded grafts involves a level of cell proliferation, the synthesis and deposition of extracellular matrix proteins is also a ubiquitous observation in these grafts. To assess the composition of midgraft neointima in sodded grafts, a morphometric method was developed to provide a differential quantitation of the cellular-hyperplastic and extracellular-hypertrophic elements of intimal thickening. The formed neointima on microvessel endothelial cell sodded and control (noncell-treated) ePTFE vascular grafts was quantified after 3, 12, and 52 wk of graft implantation in a canine carotid artery model. Midgraft sections of grafts were evaluated for both intimal thickness (IT) and cell density per unit volume and quantified using a PC-based image analysis program, Sodded grafts explanted at 3 wk exhibited an average neointimal cell density (3 x 10(9) cells/cm(3); IT 30 mu m) equivalent to cell densities observed in normal arterial media, After 12 wk the mean cell density approached a hyperplastic value (3.7 x 10(9) cells/cm(3); IT 76 mu m), while grafts explanted after 52 wk exhibited a mean cell density (2.8 x 10(9) cells/cm(3); IT 30 mu m) similar to 3-wk values, Control grafts that received no cells exhibited no midgraft cellular coverage, These results indicate that neointima formation in the midgraft region of sodded grafts occurred via mechanisms involving both a cellular hyperplasia and an extracellular hypertrophy, Differential responses occur presumably due to localized differences in cellular proliferation and cellular biosynthetic activity.