Some effects of liposome-incorporated amphotericin B on the permeability of the human erythrocyte membrane to potassium and sodium ions is reported. The influence of cholesterol and amphotericin B in causing a shift towards smaller and larger liposomes, respectively, is also described. Phosphatidylcholine liposomes containing amphotericin B in a molar ratio of 7.4 +/- 0.1 (mean +/- SD) antibiotic to 1000 phospholipid reduced the initial rates of K+ and Na+ transport across the erythrocyte membrane to 40 +/- 2.6% and 0%, respectively, of their rates in the presence of comparable concentrations of free amphotericin B. Amphotericin B incorporated into liposomes (8.2 +/- 0.15 mumol antibiotic per 1000 mumol total lipid) composed of cholesterol and phosphatidylcholine (in a molar ratio of 3:7) reduced the initial rate of K+ transport to 19 +/- 0.8% of its value measured in the presence of a comparable concentration of free antibiotic. These results suggest that liposomes containing specified amounts of amphotericin B, especially liposomes also containing cholesterol in addition to phosphatidylcholine, could be used as a method of controlling K+ transport across the erythrocyte and possibly other types of cellular membranes, thereby limiting antibiotic toxicity to some mammalian tissues.