As the genetic diversity of Plasmodium falciparum infections in humans is implicated in the pathogenesis of malaria, the association between P. falciparum diversity at the merozoite surface protein-2 (msp2) locus and the severity of childhood malaria was investigated in Ibadan, in south-western Nigeria. The 400 children enrolled had acute uncomplicated malaria (144), cerebral malaria (64), severe malarial anaemia (67) or asymptomatic infections with P. falciparum (125). Nested PCR was used to investigate the msp2 genotype(s) of the parasites infecting each child. In terms of the complexity of infection and frequency of polyinfection, the children with asymptomatic infection were significantly different from those with uncomplicated malaria or severe malaria. The median number of FC27 alleles detected was higher in the asymptomatic children than in the symptomatic. After controlling for age and level of parasitaemia (with 'asymptomatic infection' as the reference category), a child in whom no FC27 alleles were detected was found to be at five-fold greater risk of uncomplicated malaria, and a child without polyinfection was found to have a three-fold increased risk of severe malarial anaemia and a six-fold increased risk of cerebral malaria. It therefore appears that msp2 genotypes are associated with asymptomatic carriage and that children with mono-infections are more likely to develop severe malaria than children with polyinfection.