Lipid turnover and deposition is under the control of developmental, nutritional, metabolic and neuroendocrine influences. The aim of the current investigations was focused on the study of the involvement of leptin and neuropeptide Y in lipid mobilization. The lipolytic rate was assessed through glycerol release after incubation with leptin and NPY at concentrations ranging from 10(-6) to 10(-12) M in isolated adipocytes obtained from female rats. The presence of leptin at concentrations of 10(-12) to 10(-7) M in the incubation medium of isolated fat cells significantly increased (p < 0.0001) glycerol release, except at the concentration of 10(-11) M, where the increase was (p < 0.01) as compared to the basal lipolytic activity. On the other hand, isolated fat cells of Wistar rats bathed in 10(-10) to 10(-6) M concentrations of NPY demonstrated a statistically significant decrease (p < 0.0001) in glycerol release. At equimolar concentrations of leptin and NPY (10(-12) to 10(-6) M) the observed lipolytic activity is comparable to the basal lipolytic activity, except at a concentration of 10(-9) M where upon a significant increase in lipolysis is observed. A further increase in the equimolar concentrations, beyond 10(-9) M results in a return to the basal lipolytic activity. Summing up, new evidence suggests that NPY and leptin may interact in a homeostatic loop to regulate body-fat mass and energy balance not only at the central nervous system level, but also directly at the adipocyte level.