The occurence, distribution, and ultrastructural morphology of microfilaments in malignant epithelial cells of invasive squamous cell carcinoma of human oral cavity were studied by electron microscopy. The findings are compared with those in malignant oral epithelial cells of carcinoma-in-situ. In the malignant cells of invasive carcinoma, microfilaments 50-70 A in diameter are prominent in the cortical cytoplasm of the lateral and basal cell surfaces, adjacent and parallel to the plasma membrane, and extending into cell processes and microvillous extensions. Additional microfilaments are found to run from the peripheral cytoplasm to the perinuclear region. The microfilaments are aggregated into bundles aligned parallel to the long axis of the cell and display foci of increased electron density. They also tend to be aggregated into complex polygonal arrays. These microfilaments are similar in organization, concentration and ultrastructural architecture to those of various other nonmuscle cells, where they are thought to be capable of contraction and associated with cell motility. The presence of a microfilament system believed to be associated with contractile and motile cell processes may be an important characteristic of malignant cells of invasive tumors. The lack of abundant organized microfilaments in malignant cells in the absence of tumor invasion, and the presence of a prominent microfilament system in cells of invasive tumors, suggest that the microfilaments are related to the invasive properties of malignant tumor cells.