The role of the cytoskeleton during viral infection is poorly understood. Here we show, using a combination of mutant and drug studies, that the intracellular enveloped form of vaccinia virus is capable of inducing the formation of actin tails that are strikingly similar to those seen in Listeria, Shigella and Rickettsia infections. Analysis using video microscopy reveals that single viral particles are propelled in vivo on the tip of actin tails, at a speed of 2.8 mumol min-1. On contact with the cell surface, virus particles extend outwards on actin projections at a similar rate, to contact and infect neighboring cells. Given the similarities between the motility of vaccinia virus and bacterial pathogens, we suggest that intracellular pathogens have developed a common mechanism to exploit the actin cytoskeleton as a means to facilitate their direct spread between cells.