SUMMARYIn mice, intravenous inoculation of relatively avirulent strains of herpes simplex virus [e.g. P2C6, a mutant of strain CL(101), deficient in thymidine kinase] produced infection in the adrenal gland and mid-spinal cord followed by hind limb paralysis without death. Male mice were less susceptible to paralysis than female mice. Castration of male mice before inoculation increased their susceptibility to that of female animals; treatment with testosterone reversed this change. The differences in susceptibility to paralysis in the various categories of animal were not reflected in differences in growth of virus in the adrenal gland or spinal cord.Experiments on herpes simplex virus (HSV) viraemia of mice established by intravenous (i.v.) inoculation have revealed the extreme susceptibility of the adrenal gland to infection (Hill et al., 1986). Moreover, infection of the gland provides a route for entry of virus into the lower thoracic spinal cord. Such involvement of the spinal cord is associated with demyelination and hind limb paralysis. After i.v, inoculation of relatively avirulent strains of HSV the incidence of hind limb paralysis can be high, particularly in female mice, but all animals survive. However, male mice show a considerably lower incidence of this paralysis. We now report observations on the effect of male sex hormones on the incidence and severity of the paralysis and on the replication of HSV type 1 (HSV