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Blood mononuclear cells (BMNC) were isolated from sickle cell trait (HbAS) healthy donors and normal haemoglobin (HbAA) healthy donors resident in a P. falciparum endemic area of eastern Sudan. Blood samples were collected during the malaria season. BMNC were tested for their proliferative responses to phytohaemagglutinin (PHA), purified protein derivative of tuberculin (PPD) and to soluble P. falciparum antigens (SPAg). Higher responses to SPAg and PPD were observed in the HbAS children compared with the HbAA children, whereas no differences were observed among adults of the two phenotypes. Proliferative responses to PHA were comparable in all individuals tested. The significance of these findings in relation to haemoglobin phenotype, age and the possible immunoregulatory mechanisms operating in HbAS and HbAA children during the malaria season is discussed.