Autopsy samples from the brains of 20 patients who died of falciparum malaria were examined by light microscopy and by an immunohistologic method. Particular attention was paid to a comparison of the pathologic features of the white matter and the cortex. In the high-sequestration (> 50%) group (n = 8), the mean ± SD percentage of cerebral microvessels that showed parasitized red blood cell (PRBC) sequestration was 71.2 ± 8.1% in the cortex and 84.0 ± 6.7% in the white matter. The difference in the PRBC sequestration rate between cortex and white matter was statistically significant (P < 0.01). Perivascular and ring hemorrhages were seen more frequently in the white matter than in the cortex. Deposition of IgG and Plasmodium falciparum antigen in the cerebral microvessels was more highly significant in the white matter than in the cortex (P < 0.01). Our study demonstrated that the localized concentration of PRBC sequestration in the brain correlated with the marked immunohistologic differences in the microvessels of cortex and white matter.