The interaction of Salmonella typhimurium 395 MS and its rough Rd-mutant 395 MR10 with HeLa cells was studied by transmission and scanning electron microscopy. The bacteria attached to central as well as more marginal positions of the HeLa cell surface. Bacteria associated preferentially to HeLa cells with a relatively low number of microvilli, in which they often were entangled. Bacteria attached to the cell border were sometimes surrounded by membrane folds, possibly as a response to their attachment. Infected cells had longer and more slender microvilli compared with noninfected cells. Some parts of the attached bacteria were in close contact with the HeLa cell membrane, whereas other parts were separated from the latter by a gap. Bacteria adhered preferentially to microvilli without obvious membrane damage. Most of the intracellular bacteria were surrounded by a membrane, often appearing as a vacuole, which sometimes contained more than one bacterium. Intracellular bacteria seemed to be morphologically intact. We propose that S. typhimurium enter HeLa cells by a process of phagocytosis.