Electron microscopy of intact tissue and cultured smooth muscle suggested the occurrence of phagocytosis of necrotic cells by normal vascular smooth muscle cells. Phagocytosis was further studied in vitro in muscle cells from guinea pig aorta, guinea pig vas deferens, and striated muscle from chick embryo by light and electron microscopy. The uptake of yeast cells (approximately 2-mum. diameter) into living cultured smooth muscle cells from guinea pig aorta was observed with phase contrast microscopy and differential interference (Nomarski) optics. Periodic acid-Schiff staining showed the yeast cells lined up in the cytoplasm of the muscle cells. Electron microscopy confirmed the uptake of yeast cells by differentiated muscle cells. Some of the yeast in the smooth muscle cells showed signs of disintegration suggesting digestion within the phagosome. Spontaneously contracting cultured smooth, cardiac and skeletal muscle cells incubated with latex spheres (0.3-mum. diameter) showed uptake and sequestration of the spheres. The ability of muscle cells to phagocytose necrotic cells and other particulate matter may be important in atherogenesis and in the repair of tissue after injury.