SummaryThere is evidence that autoimmune aberrations may contribute to the immunopathological consequences of Chagas' disease and because of this we sought to determine whether four inbred strains of mice bearing the single autosomal recessive gene, lpr (lymphoproliferation), which controls certain autoimmune manifestations, are particularly susceptible to acute infection with the Y strain of Trypanosoma cruzi. MRL/MpJ‐lpr/lpr, C57B1/6J‐lpr/lpr, AKR/J‐lpr/lpr, C3H/HeJ‐lpr/lpr showed parasitaemias 2–10 times higher when compared to their congenic partners. Mortality was significantly higher in three of the four lpr strains. The results indicate that a single autosomal recessive gene which is associated with autoimmunity can influence susceptibility to acute T. cruzi infectio