Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentiation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na-K-acetate (300-600 mOsm/kg H2O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represented 3 very distinct populations with respect to total plasma IgE content, medians were less than 0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml; respectively. Increasing osmolarity to 500 mOsm/kg H2O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H2O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsm/kg H2O. Responses were highly correlated to results at 300 mOsm/kg H2O. The use of 600 mOsm/kg H2O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by increased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays used in allergy diagnosis.