Intravenous administration of heterologous anti-thymocyte antibodies, which react with rat mesangial cells, induced minimal mesangiolysis (6 hours to 3 days) followed by mesangial hypercellularity. Moreover, autologous immunoglobulins appeared in the mesangium within 1 or 2 weeks. At the same time, electron microscopy demonstrated mesangial deposits. Accompanying these pathological alterations, significant proteinuria developed. To accelerate an acute autologous immune reaction, rats were preimmunized with rabbit IgG prior to the injection of anti-thymocyte antibodies. They revealed marked mesangiolytic lesions 3 days after injection with deposition of autologous immunoglobulins and C 3 in the mesangium. In contrast, there was no significant proteinuria. Thus, mild pathological alterations in the mesangium induced by heterologous and subsequent autologous immune reactions caused proteinuria, and accelerated immune injury to the mesangium produced severe mesangiolysis without proteinuria. Based on these findings, it is suggested that the time-lapse between heterologous and autologous immune reactions to the mesangium influences the pathological alterations and clinical manifestations occurring in mesangial injury by anti-thymocyte antibody.