Cysteine auxotrophy and absence of cystathionase (CSE) has been associated with certain human and rodent leukemic cell lines. To determine whether this state was a marker of malignant transformation or of cellular differentiation, CSE content was measured in 16 well characterized human leukemia-lymphoma cell lines. Enzyme was easily detected in several lines but its level did not correlate with a proposed scheme of differentiation based on cell-surface markers. However, the apparent absence of enzyme in human bone marrow CFU-C determined by growth experiments suggests reduced levels of CSE may be a marker of cytoplasmic immaturity.