The invention provides a method of treating or preventing ischemia-reperfusion injury of the kidney in a mammal. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (p.sub.m) and the total number of amino acid residues (r) wherein 3p.sub.m is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p.sub.t) wherein 2 a is the largest number that is less than or equal to p.sub.t+1, except that when a is 1, p.sub.t may also be 1.