The ability of several strains and recombinants of herpes simplex virus 1 (HSV-1) to proliferate in the adrenal glands and to invade the spinal cord was studied. After intraperitoneal infection, pathogenic HSV-1 strains replicated in the adrenal glands, penetrated the spinal cord and migrated to the brain. The nonpathogenic strain HFEM could not replicate in the adrenal glands, but the recombinant virus MLC1 was able to do so after rescue by reinsertion of the HpaI-P sequence into the BamHI fragment of HFEM DNA. However the recombinant MLC1 virus could not penetrate the spinal cord. The effect of HSV-1 infection on the expression of the cellular genes for multidrug resistance (in the adrenal glands) and proenkephalin A (in the spinal cord) was also studied.