Insulin-dependent diabetes mellitus appears to be an autoimmune disease that is characterized morphologically by insulitis, an inflammation of the pancreatic islets of Langerhans that results in the destruction of the insulin-producing beta cells. The RT6-depleted DR rat provides a good model for the in situ study of insulitis. The authors used the anti-RT6.1 monoclonal antibody to selectively deplete RT6 T cells in DR rats and produce a synchronous and rapid development of insulitis that commences 10 days after treatment. The phenotype of cells that infiltrated the islets at different stages of insulitis in the RT6-depleted DR rat was determined by immunocytochemical techniques. A prodromal period of 10 days was present in which the authors could not detect morphologic alterations within the pancreas. This is followed by a second phase of early insulitis in which a few islets are infiltrated by macrophages and T cells. This rapidly progresses by 18 days to the final phase of generalized insulitis in which the islets are massively infiltrated by macrophages and T cells.