Smooth muscle cells (SMC) of normal and varicose human saphenous intima were studied on cryostat sections by immunohistochemistry with alpha-smooth muscle actin (ASMA), type IV collagen, and laminin antibodies and also by transmission electron microscopy. The findings suggest two structurally distinct subtypes of smooth muscle cells with thin and thicker external lamina. Thin external lamina SMC were characterized by laminin, type IV collagen, weaker external lamina reactivity, and intense cytoplasmic alpha-smooth muscle actin immunoreactivity. Ultrastructurally, they exhibited abundant cytoplasmic microfilaments and thin external lamina. These cells were found isolated or, more frequently, clustered in fascicles close to the subendothelium in focal or zonal cushions, or in diffuse enlargement of the intima. In contrast, thicker external lamina smooth muscle cells were intensely immunolabeled for laminin and collagen IV, showing irregular cytoplasmic ASMA reaction. Single or clustered thicker external lamina SMC were seen predominantly in zonal cushions and in intima diffuse enlargement. It is very likely that these cells secrete these matrices in a nonpolarized fashion. The thicker external lamina of these SMCs showed a fine granular amorphous aspect sometimes intermingled with microfibrils. These external lamina were interposed between neighboring cells and exposed to collagen fibrils and elastic fibers. The cells also exhibited rarefaction of the cytoplasmic filaments. Intermediary cells exhibiting both features were rarely seen. Thicker external lamina SMC should be discussed in the context of an adaptive/proliferative response leading to dysfunction of the fibroelastic properties of the vein wall.