PURPOSE: To describe, by in vivo confocal microscopy, the structural changes occurring during the course of adenovirus epidemic keratoconjunctivitis (EKC), from the onset of the disease up to 24 weeks of follow-up. METHODS: Eight patients (age, 8-57 years) with clinical evidence of EKC were examined and photographed in vivo with a Heidelberg Retina Tomograph II, Rostock Cornea Module. RESULTS: At 1 week, confocal microscopy revealed clusters of hyperreflective cells in the basal epithelial cell layer. In these sites, we observed subepithelial accumulations of dendritic cells, located mainly at the level of the Bowman layer. Underneath in the anterior stroma, we detected clusters of highly reflective, irregularly shaped cells. At 2 weeks, all patients presented follicular conjunctivitis, focal keratitis, and subepithelial infiltrates. At this point, confocal microscopy revealed persistent clusters of hyperreflective basal epithelial cells intermingled with roundish cells that probably represent leukocytes. Underneath, dendritic cells had formed an intricate network and, in the anterior stroma, we detected a hyperreflective cellular plaque that corresponded to the subepithelial infiltrate. At 24 weeks after onset of the symptoms, density and dimension of dendritic cell clusters were decreased, but we now detected stromal hyperreflectivity in the midstroma. CONCLUSIONS: In vivo confocal microscopic examination of subepithelial infiltrates appearing during EKC suggests that the innate immune system, as represented by the dendritic cells, is highly active early on. Nonetheless, the inflammatory component in both epithelium and stroma is massive and, in deeper stromal layers, long standing.