Staining patterns for nonspecific esterase (NSE) were analyzed retrospectively in 14 cases of acute monocytic leukemia (M5) using alpha-naphthyl acetate as substrate. An attempt was made to correlate variability in NSE activity with clinical findings. Two staining patterns were distinguished: (1) diffuse fine granular cytoplasmic staining, and (2) dense focal staining superimposed on a weak positive cytoplasmic background. The 14 cases were divided into two groups according to their different staining qualities: Group 1 (6) diffuse and Group 2 (8) focal. All six cases of Group 1 were typical hypercellular acute leukemias. Group 2 contained four cases of hypercellular acute leukemia and four cases of hypocellular acute leukemia. All the cases of hypocellular leukemia showed the pattern of focal NSE activity. No difference in the clinical presentation or course of the disease between Groups 1 and 2 was found.