The histopathology of a granulosis virus (GV) isolated from the western grapeleaf skeletonizer, Harrisina brillians (Lepidoptera; Zygaenidae), was studied in histological sections and wet mounts of this species. In contrast to all other known GVs, the principal site of infection for this virus was the midgut epithelium. In fourth instars exposed to virus, infection resulted in almost complete destruction of the midgut epithelium and host death by 6 days post-treatment. Infected gut cells in both larvae and adults supported complete replication of the virus, including the production and occlusion of virions. After infection, epithelial cells detached from the basement membrane and sloughed into the midgut lumen. Many larvae developed a diarrhea 2 to 4 days after infection which contained feces highly infectious to other larvae. Electron microscopy confirmed the presence of intact GV in these feces. The meconium collected from adults which survived infection as larvae was also highly infectious. These results suggest that horizontal and vertical routes of transmission made possible by the replication of this GV in the midgut epithelium contribute substantially to its ability to spread quickly throughout and decimate populations of H. brillians. Despite its atypical biology, the physical characteristics of this GV were similar to those of other GVs. The occlusion bodies were granular in shape, approximately 150 × 300–400 nm in size, and contained virions of averaging 80 × 200 nm. The estimated size of the genome was 120 kb pairs based on fragments generated by digestion of the viral DNA with the restriction endonucleases EcoRI and HindIII.