Inbred BALB/c (H-2d), CBA (H-2k) and C57B1/6 (H-2b) mice immunized with Plasmodium falciparum schizonts or culture supernates develop antibodies of different antigenic specificities. It has been observed that C57B1/6 mice were unable to produce detectable antibodies against the p126 antigen (native molecule and p73 or p50 processed fragments) compared with other inbred mice. Similar results were obtained using BALB congenic mice with a lack of p126 antibody response in H-2b mice, while H-2d and H-2k mice produced antibodies against the p126. Lymphocyte proliferation assays performed by incubation of spleen cells with immunopurified p126 were positive for immunized BALB/c (H-2d) and congenic H-2d or H-2k mice. On the other hand, no lymphocyte stimulation was observed with either C57B1/6 (H-2b) or congenic H-2b mice. These results suggest an MHC restriction of the immune response against the entire p126 (found in schizonts) and its p73 and p50 naturally processed fragments (found in culture supernates).