When mouse fibroblast L-929 cells were pre-infected with vesicular stomatitis virus, an enhancement of invasiveness by Salmonella typhimurium was observed. The effect was more pronounced when higher virus doses were used. Short-time (5 h) pre-incubation with virus caused a moderate enhancement of invasiveness. When virus pre-incubation time was increased to 8 h or 13 h, a further enhancement was observed. Results obtained after pre-incubation with UV inactivated virus were similar to that achieved by the short-time pre-incubation with the corresponding viable virus preparation. This indicates (i) an early phase of virus infection, when virus causes enhancement of invasiveness that is not dependent on viral nucleic acid induced metabolism, and (ii) a later phase, when virus-induced metabolism is necessary for the enhancement. When virus and bacteria were given concomitantly to infant mice, lethality was increased compared to groups that only received virus or bacteria. The data indicate that vesicular stomatitis virus aggravates infection with a facultatively intracellular bacterium, partly by enhancing the invasiveness of the bacteria.