Swelling-activated K flux was investigated in erythrocytes from patients on regular hemodialysis. K influx, measured by 86Rb uptake, was increased in hemodialysis patients from 25.5 ± 0.6 to 47.3 ± 3.4 nmol/109cells/h (n = 4, p < 0.01), when the medium osmolarity of Hepes buffer was decreased by 100 mosm/kg H20. In normal subjects, K influx was also stimulated from 28.1 ± 1.2 to 37.8 ± 2.1 nmol/l09cells/h (n = 4, p < 0.01). The swelling-activated increment of K influx was comparatively higher in hemodialysis patients (85.5 vs. 34.5% in controls). Reduction of the medium osmolarity by 100 mosm/kg H2O also caused a larger increase of K efflux in hemodialysis patients than in control subjects (171.1 vs. 118.1%). K efflux was increased even in the presence of 10-4M ouabain (from 284 ± 25 to 879 ± 122 nmol/109cells/h), although the increment of K efflux was completely abolished when Cl was replaced by gluconate (555 ± 47 nmol/109cells/h with Cl and 467 ± 44 nmol/109cells/h without Cl). These data suggest that in hemodialysis patients, swelling-activated K transport is enhanced via activation of the Cl-dependent ouabain-insensitive K transport