This paper describes immune responses to P. falciparum infection in individuals living in an area of highly seasonal, unstable malaria transmission. The in vitro cellular immune responses of peripheral blood mononuclear cells (PBMC) from 36 Sudanese donors to a complex of affinity purified soluble P. falciparum antigens (SPag) and two components thereof (Ag1 and Ag7) were examined and compared to humoral immune parameters. In 29/36 Sudanese donors, SPag induced a significant lymphoproliferative response in vitro. In contrast only 3/27 Danish donors never exposed to malaria responded to SPag. Ag1 and Ag7 induced significant lymphoproliferation in 9/34 and 13/36 Sudanese donors respectively, whereas no Danish donors responded. Significant interferon-gamma production was observed in 16/27, 1/5 and 3/12 Sudanese donors when stimulated by SPag, Ag1 and Ag7 respectively. Lymphoproliferative responses to SPag correlated with proliferative responses to Ag1 and Ag7, and with Spag-induced interferon-gamma production. These results indicate that T-cell clones recognizing epitopes on Ag1 and Ag7 have been expanded in the studied population as a result of exposure to P. falciparum infection. The T-cell parameters did not correlate with the presence of antibodies to SPag, Pf155/RESA or a crude parasite sonicate or with the schizont IFA titers of the plasma. This indicates that parameters outside the degree of exposure to P. falciparum influence the cellular immune responses to malaria.