Structural changes in stromal cells during the development of human colorectal carcinomas were studied by light and electron microscopy. The results were as follows: Stromal cells of the lamina propria in control subjects consisted principally of resting fibroblasts. Stromal fibroblasts were mildy activated in adenomas with mild -moderate atypia, and more markedly in adenomas with severe atypia (carcinoma in situ). In invasive adenocarcinomas, (a) desmoplastic reaction was induced, (b) stromal fibroblasts proliferated significantly and were activated showing enlarged nuclei and abundant rough endoplasmic reticulum, and (c) some smooth muscle cells were endowed with well-developed rough endoplasmic reticulum in their axial cytoplasm, resulting in a similar appearance to "myofibroblasts". Stromal fibroblasts in ulcerative colitis and proctitis were also activated. Morphometric analysis revealed that activated fibroblasts significantly increased the areas of their nuclei and cytoplasm, and the perimeter of rough endoplasmic reticulum. These activated fibroblasts suggested a higher production of collagen and other connective tissue proteins. Bundles of microfilaments of actin type were readily found in fibroblasts in all cases examined. These filaments were most remarkable in the fibroblasts in the desmoplastic stroma of invasive adenocarcinoma and were considered to be one of the basic components of these cells. Relationships between fibroblasts, "myofibroblasts", and smooth muscle cells are discussed.