Virologic events in the pathogenesis of scrapie in the goat were studied after intracerebral and sc inoculation of mouse-adapted scrapie virus. In goats inoculated sc with about one goat id50, virus was first detected in lymphatic tissue, mainly lymph nodes. After many months, virus appeared in the central nervous system, particularly the spinal cord and brain stem, where maximal concentrations of virus were attained. Clinical signs of scrapie appeared when the concentration of virus in the diencephalon, brain stem, and cerebellar cortex reached about 3 log10 mouse intracerebral ld50 per 30 mg of tissue. Concentrations of virus in nonneural tissues were generally low. Late in the course of infection after sc inoculation, virus disappeared from lymphatic tissues. Because only small amounts of virus were irregularly present in tissues that might allow its egress from the host, goat-to-goat transmission appears unlikely. For this reason, scrapie virus probably cannot be maintained in goats isolated from infected sheep.