AbstractSoluble phospholipase A2activity was characterized in two human monocytic cell lines, U937 and Mono Mac 6. The enzyme showed an absolute requirement for Ca++, an alkaline pH optimum and Michaelis‐Menten kinetics in both cell lines. Differentiation of U937 and Mono Mac 6 cells with 1,25 (OH)2vitamin D3(10 nM, 72 h) enhanced PLA2activity by 82 per cent and 56 per cent, respectively. Furthermore, kinetic experiments revealed that enzyme activity increased within 3 h when cells were brought from the nonproliferative phase of growth to the start of a new cycle of cell proliferation. This initial activation of PLA2could be inhibited by cycloheximide and actinomycin D, indicating the requirement of gene transcription. Taken together, these results suggest a role of cytosolic, Ca++‐dependent PLA2in differentiation and growth of monocytic ce