To study the relevance of polyclonal B cell activation (PBA) associated with malaria in the development of specific anti-sporozoite immunity, we used a reverse haemolytic plaque assay and an immunoradiometric assay employing the synthetic peptide (NANP)3, the main epitope of the circumsporozoite (CS) protein of Plasmodium falciparum, to assess respectively the degree of activation of IgG and IgM secreting cells and the level of anti-sporozoite antibodies in 95 subjects with malaria and 21 non-infected individuals. A positive correlation was observed between the anti-(NANP)3 antibody levels and the number of past attacks of malaria but not between the former and the age of individuals or the number of months of residence in the endemic region. Individuals with high numbers of IgG or IgM secreting cells (SC) had lower levels of anti-(NANP)3 antibodies; those with levels of antibodies above the mean for malaria-infected individuals had lower numbers of IgGSC and higher haematocrit and haemoglobin values. These data show the existence of a negative relationship between malaria-induced PBA and anti-sporozoite immunity, and it is suggested that either PBA blocks the development of anti-sporozoite immunity or, alternatively, the latter protects individuals against malaria and malaria-associated PBA.