Rats were infected with herpes simplex virus type I (HSV‐1) by corneal scarification. The spread of virus in the brain, the infiltration of leucocytes into infected areas, and the expression of major histocompatibility complex (MHC) glycoproteins by brain cells were assessed as a function of time by immunohistochemistry. Virus moved along neuronal pathways, achieving widespread distribution in the brain by days 8–10 when the illness appeared most severe. Granulocytes, T‐lymphocytes, and monocytes infiltrated the tissue matrix at sites of infection. Microglial cells were induced to express MHC class I and class II glycoproteins. Reactive microglia near the sites of infection most vigorously expressed such glycoproteins. At the peak of the infection they were detectable on microglia throughout the brain, including areas apparently separated from unfection. Evidence of viral antigens, as well as microglial MHC expression, had largely disappeared by day 30. Neurons, astrocytes, and oligodendroglial cells failed to express MHC antigens. Copyright © 1990 Wiley‐Liss, Inc.