SummaryThe protective effect of affinity purified antigen has been investigated in an experimental model for malaria which shows a well marked recrudescence of parasitaemia, a feature of the disease in man. A monoclonal antibody (MoAb) recognizing an epitope common to two genetically distinct cloned lines ofPlasmodium chabaudi(AS and CB). was used to purify a Mr250 000 polymorphic schizont antigen (PSA) from these parasites. The purified preparations were then examined for the presence of specific and cross‐reactive epitopes by immunoprecipilation with a panel of MoAb raised againstP. chabaudiAS. When tested previously on smears of parasitized blood by immunofluorescence, or against lysates of parasitized erythrocytes by immunoprecipitation, most of these MoAb had been found to be AS specific. When either AS or CB affinity purified Mr250 000 PSA was used as the target, these same MoAb immunoprecipitated both antigens, and in some cases, a number of associated polypeptides (AP) which co‐purify with the Mr250 000 PSA. Subsequently, mice were immunized with either the purified AS or CB antigens in Freund's complete adjuvant (FCA). Pre‐challenge sera were compared by indirect immunofluorescence and immunoprecipitation. Sera from mice immunized with AS antigen reacted strongly with AS and cross‐reacted with CB parasite preparations. Pre‐challenge serum from CB antigen immunized mice reacted well with CB, but only faintly with AS preparations. In mice immunized with the AS antigen and then challenged with either AS or CB parasites, the initial parasitaemias were delayed in appearance and the height of the peak parasitaemia reduced, an effect which was most pronounced after challenge with homologous parasites. Only homologous challenge of the mice immunized with CB antigen produced statistically significant modification of the initial parasitaemia. In the immunized mice challenged with homologous parasites, the delayed appearance and slightly reduced peak of the primary parasitaemia was associated with delayed resolution of the patent parasitaemia and significant enhancement of the recr