Complement receptor type 1 (CR1) on erythrocytes shows an inherited numerical polymorphism which correlates with a HindIII-RFLP (restriction fragment length polymorphism) of the CR1 gene in various populations. To investigate the relationship between CR1 density polymorphism and disease severity, we typed 185 Thai patients with acute falciparum malaria (55 severe and 130 uncomplicated) for their genotypes of this polymorphism. The level of expression of erythrocyte CR1 from 42 randomly selected patients was measured by enzyme-linked immunosorbent assay (ELISA). We observed a significantly higher frequency of homozygotes of the CR1 low density allele (LL) among the severe group as compared to the uncomplicated group (P = 0.005). CR1 expression on erythrocytes from patients with the LL genotype was significantly lower than homozygotes with the high density allele (HH) (P < 0.0001) and heterozygotes (HL) (P = 0.013). The results suggest that a genetically-determined low CR1 density on erythrocytes may be a risk factor for developing a more severe form of malaria in Thai subjects.