The role of genetic factors in determining the clinical response of children to Plasmodium falciparum infection is not fully understood. A longitudinal survey of malaria morbidity in a cohort of 258 pairs of twin children was conducted in a rural area of Gambia to assess the extent to which genetic factors determine the host's susceptibility and clinical response to infection. The marginal correlation (which measures the excess probability of both twins being affected above that expected assuming independence) for malaria was higher in dizygous (DZ) than in monozygous (MZ) twin pairs, indicating that infection per se is largely determined by environmental factors. Once infected however, both members of an MZ pair were more likely to develop fever than were twins of a DZ pair, suggesting that genetic factors influence the presentation of clinical disease.