In the search for antibodies correlating with host-protective immunity to Plasmodium falciparum in man, sera from individuals in Papua New Guinea were analyzed at the time of infection and in the convalescent period following infection. Titers of antibody were determined by enzyme linked immunoassay (ELISA), and the specificities of antibodies was examined by gel electrophoresis of immunoprecipitates. In the majority of cases, convalescence was associated with an increase in antibody titer and one-dimensional gel analysis of immunoprecipitated biosynthetically labeled parasite antigens demonstrated the variability in specificity of the antibody response in the two types of serum samples from different individuals. A protein of Mr 96,000 which has previously been identified as a candidate host-protective antigen was not clearly seen in immunoprecipitates generated with acute serum, even in samples with high titers of antibody assessed by ELISA. Antibodies to a protein Mr 96,000 were present in some, but not all convalescent sera. Two-dimensional gel analysis was more sensitive in detecting a boost in antibody response to minor antigens (e.g., an acidic protein Mr ≅ 230,000). This approach has not led to identification of antibody specificities to major antigens which are invariably boosted by infection and drug cure, but has identified antibody specificities in acute sera which are inadequate in quantity or quality to inhibit parasite growth.