The pathologic response of New Zealand White rabbits to experimental infection with Trypanosoma rhodesiense is described. Autopsies of 18 rabbits killed from 30–44 days after infection revealed focal perivascular inflammation of the ears, eyes, and testes. Examination by electron microscopy revealed extravascular trypanosomes in the dermis of the ear and interstitium of testes. Deposits of IgG, IgM and C3 were in renal glomeruli associated with glomerular hypercellularity; proteinuria was present as evidenced by an increase in tubular hyaline droplets. There was marked hyperplasia of lymph nodes and spleen with generalized increase in the number of macrophage and plasma cells. In contrast there was thymic atrophy. The findings suggest an immunologic host response associated with severe localized vascular injury.