In order to develop a nonmetabolizable analog of glucocerebroside to investigate the distribution and accumulation of this lipid in model systems, thiohemiacetal derivatives were synthesized and their susceptibility to enzymatic hydrolysis by purified human placental glucocerebrosidase was examined. Sulfur analogs were found to be completely refractory to the activity of this enzyme, indicating their potential use in animal and isolated cell models and possibly for the preparation of affinity chromatography columns for the isolation of glucocerebrosidase.