OBJECTIVE Progressive outer retinal necrosis syndrome is a devastating retinopathy seen primarily in patients with acquired immune deficiency syndrome. To provide additional details of the pathogenesis of this disease, the authors describe the evolution of clinical and fluorescein angiographic changes during the course of progressive outer retinal necrosis syndrome. METHODS The authors performed serial clinical examinations, fundus photography, and fluorescein angiography in a patient with acquired immune deficiency syndrome with progressive outer retinal necrosis syndrome. Clinical and fluorescein angiographic findings were correlated to provide detailed sequential analysis of the pathologic changes occurring during the course of this disorder. RESULTS The angiographic changes seen during the various stages of the disease consisted of zonal microvascular alterations, retinal pigment epithelium (RPE) destruction, and choroidal leakage. Retinal damage was correlated closely with regions of choroidal leakage and was clinically evident as outer retinal whitening. Disease reactivation occurred as a prominent brush-fire border of intense leakage involving the retina, RPE, and choroid. Extensive damage to the retinal vasculature and RPE was noted in the wake of clinical infection. CONCLUSIONS The angiographic findings in our patient demonstrate that the progressive outer retinal necrosis syndrome is a retinochoroiditis that involves the full thickness of retina as well as the RPE and choroid. The inflammatory changes seen throughout the course of this disease correlate with the histopathologic patterns reported to date.