The role of disulfide-dependent protein conformation of the 195,000 kDa Plasmodium falciparum merozoite surface glycoprotein in the induction of biologically active antibodies was investigated. Serum samples from rabbits immunized with native gp195 had a mean ELISA titre of 1/560,000 and a mean in vitro parasite growth inhibition of 80%. In contrast, serum samples from rabbits immunized with reduced and alkylated gp195 had a mean antibody titre of 1/23,100 and did not inhibit parasite growth. These results indicate that the native structure of gp195 is essential for antigenicity, immunogenicity and induction of growth-inhibitory antibodies. Therefore, effective recombinant gp195-based vaccines may require the production of properly folded molecules resembling the native conformation.