The genetic determinants of lysosomal enzymes and lysosomal disorders will be examined, principally by use of somatic cell hybridization. Electrophoresis systems capable of separating the lysosomal enzymes in hybrid cells and specific histochemical stains capable of detecting the various lysosomal enzymes after electrophoresis will be developed. These techniques will be used to assign the genetic determinants for lysosomal enzymes and disorders to specific human and murine chromosomes. This approach will be used to assess both the determinants of enzyme structure (structural genes) and any genetic factors which modify or regulate the expression of the structural genes. Somatic cell hybridation will also be used to analyze, by complementation, the genetic similarity or dissimilarity of the various types of "Chediak-Higashi" disorders known in man and other animals (mice, mink, cattle, and cats).