Staphylococcus aureus plays an important role as a bacterial pathogen after traumatic injury. The majority of isolated strains produces alpha-toxin, a 33-kDa protein, with membrane-damaging and lethal effects. The central nervous system (CNS) has been considered as the possible target for the lethal action of this toxin. A transfer of alpha-toxin across an intact blood-brain barrier (BBB) is however unlikely. The aim of the present study was to determine if alpha-toxin is accumulated in CNS regions which lack the BBB function. The distribution of alpha-toxin after intravascular injections, in normal mice and rats as well as in rats subjected to ventral root replantation, was assessed using immunogold technique. The results show that, although alpha-toxin does not cross the BBB, alpha-toxin-like immunoreactivity could be detected in the area postrema and at the optic nerve-retinal junction. Extravasation of alpha-toxin was also shown to occur in the spinal cord even 22 months after ventral root replantation. This finding suggests that axon regeneration after ventral root replantation takes place in a macromolecular environment which is totally different from the normal CNS. The implications of vascular spread of alpha-toxin to regions devoid of BBB function are discussed in relation to the bacterial infections which might complicate severe spinal injuries.