Cross-reacting material (CRM) to human beta-D-glucocerebrosidase has been demonstrated in circulating mononuclear white blood cells of normal controls, heterozygotes, and homozygotes for Gaucher's disease. The major CRM in both normal and mutant cells corresponds to a species with Mr approximately equal to 63,000 Da. Traces of CRM at Mr approximately equal to 61,000 and 56,000 Da are also present. In contrast, the CRM in other human tissues differs markedly from that found in circulating mononuclear cells. Evidence is presented to support the hypothesis that the CRM found in white cells is a precursor of the enzyme. The significance of these results is discussed in relation to the problems of subtype determination and heterozygote detection.