Six patients with active P. falciparum malaria (two resistant to chloroquine therapy), one with treated and apparently cured P. falciparum malaria, one with active P. vivax malaria and two controls from the same geographic area of Amazonian Brazil were studied. All malaria patients had impaired red cell deformability. This was not correlated with drug resistance or number of parasitized cells. The hypothesis is presented that the presence of parasites in red blood cells and related metabolic effects produce decreased red cell deformability and may lead to microvascular perfusion deficiencies including cerebral malaria.