A regulatory role for intracellular Ca²⁺ ([Ca²⁺]_i) in adipocyte lipogenesis, lipolysis and triglyceride accumulation has been demonstrated. Compounds acting on the pancreatic sulfonylurea receptor (SUR) to increase (e.g., glibenclamide) or decrease (e.g., diazoxide) [Ca²⁺]_i cause corresponding increases and decreases in weight gain. However, these weight gain and loss effects have been attributed to insulin release rather than to the primary effects of these compounds on the adipocyte SUR and its associated K_ATP channel. Accordingly, we have evaluated the direct role of the human adipocyte SUR in regulating adipocyte metabolism. We used RT‐PCR with primers for a highly conserved region of SUR1 to demonstrate that human adipocytes express SUR1. The PCR product was confirmed by sequence analysis and used as a probe to demonstrate adipocyte SUR1 expression by Northern blot analysis. Adipocytes exhibited glibenclamide dose‐responsive (0–20 μM) increases in [Ca²⁺]_i (P<0.05). Similarly, glibenclamide (10 μM) caused a 67% increase in adipocyte fatty acid synthase activity (P<0.001), a 48% increase in glycerol‐3‐phosphate dehydrogenase activity (P<0.01) and a 68% inhibition in lipolysis (P<0.01), whereas diazoxide (10 μM) completely prevented each of these effects. These data demonstrate that human adipocytes express a SUR that regulates [Ca²⁺]_i and, consequently, exerts coordinate control over lipogenesis and lipolysis. Accordingly, the adipocyte SUR1 may represent an important target for the development of therapeutic interventions in obesity.—Shi, H., Moustaid‐Moussa, N., Wilkison, W. O., Zemel, M. B. Role of the sulfonylurea receptor in regulating human adipocyte metabolism. FASEB J. 13, 1833–1838 (1999)