The purpose of the present investigation was to carry out a detailed histological, immunofluorescence and ultrastructural study of the renal lesions which occur during canine adenovirus (CAV) infection. An attempt was made to define the mechanisms by which the virus inflicts renal injury and in particular, to determine the role of the immune response in the development of renal lesions. It was shown that 3 main mechanisms of renal damage occurred in both experimentally induced and naturally occurring CAV infections 1. During acute systemic infection, replication of virus in glomeioilar endbthial and mesangial cells vras shown to result in lytic cellular damage and release of glomerular basement membrane antigens into the urine 2. In dogs which survived to the stage when anti-viral antibody first appeared, there was also deposition of immune complexes in the glomeruli which resulted in a proliferative glomerulonephritis. Results of immunofluorescence and elution studies indicated that- the deposited complexes were composed of viral antigen and anti-viral antibody. Furthermore, repeated inoculation of mice and dogs with virus antigen-antibody complexes prepared in vitro, resulted in similar but less severe glomerular lesions. In dogs recovering from systemic infection, there was a gradual reduction in severity of glomerulonephritiso At this stage, due to elimination of virus antigen, immune complexes were no longer present in the circulation and there was removal by mesangial cells of immune deposits already present in the glomeruli 3. However, although the glomerular lesions appeared to resolve, a percentage of dogs recovering from systemic infection developed focal interstitial nephritis in response to persistence of virus in tubular epithelium. As evidence that the interstitial cellular infiltrate represented an immunological response to the virus, anti-viral antibody production was demonstrated in plasma cells found within the lesions(c) However, the morphological appearance of the lesions, which often contained large numbers of active macrophages surrounding virus- infected- tubules, suggested that cell mediated hypersensitivity reactions may also be involved.