To study the pathogenesis of simian varicella virus (SVV) infection in its natural primate host, we inoculated adult SVV-seronegative African green monkeys intratracheally with 103–104 PFU of SVV, sacrificed them 11 days, 2, 5, 10, and 12 months postinfection (p.i.), and examined lung, liver, and ganglia for SVV DNA and RNA. PCR analysis revealed SVV DNA in ganglia and viscera at 11 days and 2, 5, and 10 months p.i. Similarly, SVV transcripts corresponding to immediate early (IE), putative early (E), and late (L) SVV open-reading frames (ORFs) were found in liver, lung, and ganglia of most monkeys at multiple intervals for the 12-month study period. SVV-specific antigens were detected in ganglia and liver during acute varicella, but not in ganglia 12 monthsp.i. Analysis of control tissue (ganglia, lung, and liver) from uninfected SVV-seronegative adult African green monkeys did not reveal SVV DNA, SVV RNA, SVV-specific antigen, or varicella-specific pathological changes. Overall, intratracheal inoculation of SVV in African green monkeys resulted in the presence of viral DNA and transcription of multiple viral genes in many tissues for months after experimental infection.