Summary: In order to determine whether the mobilization of intracellular triglycerides observed in cultured human adipocytes is associated with changes in the activities of acid and neutral lipases, the activities of both enzymes were measured weekly on cultured adipocytes for several months. The activity of acid lipase was initially very low, but rose to levels 40 times the original activity within 3 months. The activity of neutral lipase decreased rapidly within the first 2–4 weeks and remained at approximately 25% of original levels thereafter.Speculation: There is increasing evidence that the human adipocyte is highly specialized and that it is derived from a stromal precursor present in the adipose tissue. The cell has the capacity to acquire in culture the properties of the precursor, as evidenced by the appearance of acid lipase and disappearance of neutral lipase. We submit that the low level of acid lipase in the adipocyte is related to its lipid storage function. It remains to be proven that it is not primary to the differentiation of the adipocyte from its precursor. Furthermore, we speculate that a direct biochemical relationship exists between the neutral lipase and intracellular triglyceride stores in the adipocyte.