Extracorporeal circulation exposes blood to shear stress. In many studies, researchers reported effects of shear stress on morphology and function of various blood cells, but effects on cytokine synthesis have not been studied. The authors investigated the effect of shear stress on the synthesis of interleukin-1 beta, interleukin-1 alpha, tumor necrosis factor alpha, and interleukin-1 receptor antagonist by human peripheral blood mononuclear cells. Whole heparinized blood at room temperature was exposed to shear stresses of 50, 200, or 500 dyne/cm2 for 5 min or 30 sec, and to 980 dyne/cm2 for 5 sec. Peripheral blood mononuclear cells were then separated from sheared blood and cultured for 24 hrs with or without lipopolysaccharide or Staphylococcus epidermidis. Total (intra + extracellular) cytokine synthesis was measured by specific radioimmunoassay. Viability of cultured peripheral blood mononuclear cells, determined by trypan blue exclusion and lactate dehydrogenase release, was not significantly affected by shear stress. Shear stress without lipopolysaccharide or S. epidermidis stimulation did not affect synthesis of interleukin-1 or tumor necrosis factor alpha but did enhance synthesis of interleukin-1 receptor antagonist. Lipopolysaccharide- or S. epidermidis- induced synthesis of interleukin-1 was not significantly altered by shear stress. In contrast, lipopolysaccharide-induced tumor necrosis factor alpha synthesis increased with increasing shear stress and was significantly elevated over unsheared controls, whereas S. epidermidis-induced tumor necrosis factor alpha and lipopolysaccharide- or S. epidermidis-induced interleukin-1 receptor antagonist synthesis were not significantly enhanced by shear. Therefore, sublytic trauma, such as exposure to shear stress, affects in vitro responses of peripheral blood mononuclear cells to secondary stimuli.