Kanagawa-positive Vibrio parahaemolyticus adhered rapidly to suspension-grown HeLa cells and to human fetal intestinal (HFI) cells in monolayer. Kanagawa-negative V. parahaemolyticus did not adhere to HeLa cells and adhered to HFI cells at a much slower rate than Kanagawa-positive bacteria. In the HFI cell system, adherence was dependent on the presence of calcium in the incubation mixture. It was unaffected by pretreatment of the HFI cell monolayer with neuraminidase or potassium periodate. Adherence was unaffected by neuraminidase or ultraviolet irradiation of bacteria but was decreased by heat, ethanol, or periodate pretreatment. These results suggest that adherence of Kanagawa-positive V. parahaemolyticus to epithelial cells in vitro depends on interaction between the cell surface of the bacteria and the epithelial cell and that a carbohydrate on the outer membrane of the bacterial cell wall is necessary for this interaction.