In malaria-endemic areas, protective immunity is acquired gradually. Some authors have proposed that different stages can be distinguished during development. To test this hypothesis, several in vitro assays of the host immune response to P. falciparum were performed in three groups of individuals: 'unprotected' children with clinical attacks, 'semi-immune' children, without clinical attacks but with transient high parasitaemias during the transmission period, and 'protected' adults with low residual parasitaemias. By comparison of immune responses in these groups and multifactorial analyses, discriminant factors and potential protective mechanisms were identified. Anti-RESA antibody levels were lower in 'unprotected' than in 'semi-immune' children, while specific cellular responses, TNF levels and percentage of activated T lymphocytes were higher. Low humoral immunity and high cellular activation in children were followed by high humoral immunity and low cellular activation in adults. Therefore, protective immunity seems to pass through different stages and to result from the association of different immune mechanisms according to the level and duration of the individual experience of malaria.