To assess the metabolic and cardiovascular consequences of GH deficiency (GHD) on cardiovascular risk factors, we studied a homogeneous population with GHD due to a homozygous defect in the GHRH receptor gene. Anthropometric, metabolic, and cardiovascular measurements (at rest, during treadmill exercise, and during orthostatic stress) and echocardiographic data were obtained from 16 GH-naive, GH-deficient (GHD) adults and 31 age-, sex-, and body mass index-matched control (CO) subjects. The percentage of fat mass, waist to hip ratio, and total and low density lipoprotein cholesterol were higher in the GHD group. However, high density lipoprotein cholesterol, triglyceride, and fasting glucose levels were similar between groups, and fasting insulin and homeostasis model assessment of insulin resistance (HOMA(IR)) were lower in the GHD group. Systolic blood pressure (SBP) was higher in the GHD group, but no difference in diastolic blood pressure or heart rate (HR) existed. Blood pressure and HR responses to exercise did not differ between groups. During passive orthostatic stress the decrease in SBP was higher in the GHD than in the CO group, whereas an increase in diastolic blood pressure was not observed in the GHD group. Moreover, the increase in HR was blunted in the GHD compared with the CO group. Left ventricular mass and mass index were lower in the GHD group. In conclusion, this genetically homogeneous isolated GHD population presents a syndrome characterized by central obesity, dyslipidemia, and elevated SBP but reduced cardiac dimensions compared with controls.