In contrast to euthymic adult Fischer rats, immunocompromised Nu/Nu animals develop a lethal infection when inoculated with the RH strain of the protozoan Toxoplasma gondii. However, a significant period of survival is obtained when Nu/Nu rats are passively transferred with sera from 28-day infected Fischer +/+ (euthymic) animals. Specific IgE are involved since IgE-depleted sera are unable to afford such a protection. Only excreted/secreted Ag or living tachyzoites are able to induce a significant protective IgE response in intact animals. In addition, platelets or, to a lesser extent, eosinophil-rich populations from Toxoplasma infected or excreted-secreted Ag-immunized euthymic animals bear surface IgE and are cytotoxic for the parasite in vitro. Also, adoptive transfer of immune platelets confers a significant degree of protection to Toxoplasma-infected Nu/Nu animals. Our results clearly show the key role of Ag present in both living parasites and excreted-secreted Ag to induce, in this model, a protective IgE response. In addition, as in other parasitic infections, platelets and probably eosinophils are the effector cells involved in controlling parasitic dissemination during Toxoplasma infection in immunocompromised rats.