The protective effect of alpha thalassaemia (-alpha/alpha alpha) against morbidity from falciparum malaria was assessed in a prospective study of rural Gambian children. The gene frequency for single alpha-globin gene deletions was 0.12. Malariometric indices measured during cross-sectional surveys and morbidity from malaria determined by weekly surveillance were similar in children with alpha thalassaemia and in those with a normal alpha-globin genotype. However, the small number of children who carried both alpha thalassaemia and the sickle cell trait had fewer clinical episodes of malaria than children with the sickle cell trait alone. Specific antibody responses and cell-mediated immune responses in vitro to defined Plasmodium falciparum antigens were measured in children participating in the study. In general, there was no evidence of an increased prevalence or intensity of humoral or cell-mediated immune responses to the malaria antigens studied in children heterozygous for alpha thalassaemia compared with children with a normal alpha-globin genotype.