We have developed a new strain of mice homozygous for mutant alleles at both the light-ear locus on chromosome 5 and the pale-ear locus on chromosome 19. The pigmentation pattern of the double mutants, designated light-pale, is indistinguishable from the parental type. Elevated concentrations of lysosomal enzymes observed in certain tissues of the light-ear and pale-ear singly homozygous mice also are present in the double mutants, and are quantitatively indistinguishable from either parent. Although both mutations have pleiotropic effects on organelles in several tissues, neither locus influences the secretion of pancreatic zymogen granules. The close similarity in phenotypes of light ear, pale ear, and light-pale mice suggest that the le and ep loci encode different subunits of a multimeric protein, and that mutations affecting either subunit result in comparable losses of function.