Using an isolated fat cells (IFC) perifusion system and bovine growth hormone (bGH), we demonstrate that the lipolytic response in normal rat IFC is markedly enhanced after preincubation with bGH. In contrast, when IFC are prepared from diabetic animals or in the spontaneous diabetic BB rat (SDR-BB), no such preincubation is necessary. These IFC respond immediately to bGH with maximal release of glycerol. Using a binding assay established for rat growth hormone (rGH) receptors, we measured the number of GH receptors in IFC from these rats. We demonstrate a 75% increase in GH receptors after preincubation with GH in normal rat IFC, and a 125% increase in GH receptors in diabetic IFC, without preincubation. These data support the concept that enhanced sensitivity to GH is an important feature of diabetes in rats and that this sensitivity is at least in part controlled by up-regulation of GH receptors.