Normal cells are non-invasive except for a few cell types such as leukocytes and macrophages, while neoplastic cells are active in both migration and invasion. In the present investigation, the confrontations of normal rat hepatocytes, lung macrophages and B16 melanoma cells with monolayers of fibroblasts grown on collagen gel have been studied. When monolayers of fibroblasts were confronted with melanoma cells, there was obvious retraction of the fibroblasts. When hepatocytes or macrophages were seeded onto monolayers of fibroblasts, infiltration always occurred at intercellular contacts and no retraction of fibroblasts was seen. Therefore it would appear that normal and neoplastic cells penetrate into monolayers of fibroblasts by different mechanisms.