The effects of high hydrostatic pressure (up to 400 ATA) on the 'passive' (defined as ouabain + bumetanide + EGTA-insensitive) influx and efflux of radiotracer cations (K+ Rb+, Na+, Cs+) has been studied in human red cells suspended at different medium tonicities giving altered cell volumes. Under all conditions studied, cation permeability was raised at pressure, and at least two distinct components were found to comprise this flux. Thus, increasing pressure caused a generalized increase in cation permeability which was unaffected by the anion present, demonstrated linear concentration dependence, and was reduced with cell swelling, and stimulated a specific KCl pathway which was Cl- dependent, demonstrated saturation kinetics with raised [K]0 and was increased with cell swelling. High hydrostatic pressure caused a significant alteration to red cell morphology from the normal biconcave disc to cup-shaped forms and it is proposed that this is associated with the unmasking of the volume-sensitive KCl system.