To investigate the role of hemodynamics in the adherence of Plasmodium falciparum-infected erythrocytes to cerebral endothelium in vivo, we investigated cytoadherence of parasitized erythrocytes to human umbilical vein endothelial cells (HUVEC) under shear conditions in vitro. At 1.0 dyne/cm2 shear stress, parasitized red blood cell (RBC) adherence to HUVEC ranged from 9.9 ± 1.0 (± SEM) to 75.2 ± 4.8 RBC/mm2 (mean ± SEM: 35.1 ± 2.8 RBC/mm2) and was 13-fold greater than uninfected erythrocyte adherence to HUVEC (range 0.1 ± 0.1 to 6.7 ± 1.6 RBC/mm2, mean ± SEM 2.8 ± 0.8 RBC/mm2). Only erythrocytes infected with trophozoites and schizonts adhered to HUVEC under shear conditions. Parasitized erythrocyte adherence to HUVEC decreased from 28.4 ± 2.7 RBC/mm2 to 12.7 ± 2.4 RBC/mm2 when shear stress was increased from 1.0 to 2.0 dynes/cm2. At 4.0 dynes/cm2, parasitized erythrocyte adherence decreased further to 2.0 ± 1.3 RBC/mm2. In falciparum malaria patients, endothelial cytoadherence predominates in the microcirculation. Therefore, we also investigated adherence of parasitized erythrocytes to human dermal microvascular endothelial cells (MEC). At 1.0 dyne/cm2, cytoadherence of P. falciparum-infected erythrocytes to MEC ranged from 7.9 ± 1.1 to 60.0 ± 2.4 RBC/mm2 (mean ± SEM: 23.0 ± 1.7 RBC/mm2) and was 10-fold greater than uninfected erythrocyte cytoadherence to MEC (mean ± SEM: 2.2 ± 0.6 RBC/mm2). These data indicate that P. falciparum- infected erythrocytes adhere to human umbilical vein and microvascular endothelial cells under shear stress conditions typical of the postcapillary venules in vivo, and that cytoadherence is specific for parasitized erythrocytes. Furthermore, adherence only occurs within a narrow range of shear stresses, suggesting that shear stress in vivo contributes to the localization of cytoadherence to the postcapillary venules.