A previous report demonstrated that intracerebrally inoculated coronavirus produced CNS disease in two species of primates (Murray RS, Cai G-Y, Hoel K, et al., Virol 1992; 188: 274-84). We were therefore interested in testing the potential of coronaviruses to infect primate CNS tissue following peripheral inoculation. Four Owl monkeys (Aotus trivirgatus) were inoculated intranasally and ocularly and four were inoculated intravenously with coronavirus JHM OMp1 (Murray RS, Cai G-Y, Hoel K, et al., Virol 1992; 188: 274-84). Two intranasally and two intravenously inoculated animals received a second intravenous inoculum at 153 days post-infection. The animals were sacrificed 16, 35, 194, and 215 days post-infection. Tissue sections from brain and spinal cord were screened for viral products by in sity hybridization and immunostaining. Virus RNA and/or antigen was detected in the brains of all animals and the distribution corresponded to areas of inflammation and edema. Viral products were predominantly found in blood vessels and perivascular regions, suggesting hematogenous spread with entry into the central nervous system through endothelium.