Direct hemoperfusion (DHP) over an exchange resin for sodium is capable of rapidly lowering an elevated serum potassium level but has not been used clinically because of subsequent electrolyte abnormalities. After the completion of detailed in vitro studies, we developed a sodium/calcium/magnesium exchange resin mixture specifically to remove potassium from the blood. The mixture, which consisted of exchange resins for sodium (48%), calcium (48%), and magnesium (4%), gave the most satisfactory results in vitro. DHP through these resin-mixture columns for 2 h reduced elevated plasma potassium levels (6.7 +/- 1.1 to 3.5 +/- 0.6 mEq/L, p < 0.001) in anephric dogs without including any significant change in the levels of sodium, calcium, magnesium, albumin, total protein, or cholesterol. The platelet losses and changes in the plasma free hemoglobin levels observed were similar to those found with activated charcoal hemoperfusion. These results suggest that this resin hemoperfusion may be useful in patients with acute hyperkalemia.