Male (NZW x BXSB)F1 (W/BF1) mice develop immune thrombocytopenic purpura (ITP), which involves antiplatelet autoantibodies and shortened platelet life span. To determine whether reduction of dietary energy can prevent the development or reverse the progression of ITP, male W/BF1 mice were separated into five experimental groups and either given free access to semipurified diet (designated Group A, n = 50) or consumed 32% less energy from an otherwise comparable diet (Group B6, n = 20), or were initially allowed free access to diet then switched to energy restriction at ages 14, 17 or 22 wk (Groups B14, n = 10; B17, n = 20; B22, n = 20). Thrombocytopenia was prevented by energy restriction in Group B6 mice. Platelet-associated IgG (PAIgG) autoantibody levels and the number of splenic antiplatelet antibody-forming cells were low (P < 0.01) and the survival of injected IgG-coated RBC was extended in energy-restricted Group B6 mice (P < 0.01) compared with mice in Group A. Group A mice became progressively thrombocytopenic, with platelet counts as low as 34 x 10(10)/L. Progression of thrombocytopenia was reversed when energy restriction was initiated in Groups B14, B17 and B22, with platelet counts > or = 88 x 10(10)/L and reduction of PAIgG. Life span was extended among early onset energy-restricted Group B6 and Group B14 mice (P = 0.0001 and P = 0.005) but not among late onset energy-restricted Group B17 and Group B22 mice (P = 0.06 and P = 0.35) compared with Group A mice.(ABSTRACT TRUNCATED AT 250 WORDS)