It has been suggested that reduced GH secretion in Prader-Willi syndrome (PWS) may simply reflect their excessive fat body mass. However, the GH response to standard provocative tests is significantly lower in PWS adults than obese controls with similar body mass index (BMI). Nevertheless, BMI is an inadequate measure of body composition, because PWS harbor a higher percentage of fat body mass (FM%) than simple obesity, under the same degree of weight excess. This study evaluated either the GH response to combined GHRH + arginine administration and the FM%, by DEXA, in 11 PWS adults (8 females, aged 20.1-41.1 years, BMI 43.6 +/- 1.8, FM% 53.0 +/- 1.5), in comparison to those obtained in 10 patients with essential obesity (8 females, aged 23.5-45.8 years), matched for BMI and FM% (42.9 +/- 0.4 and 51.5 +/- 1.0, respectively). Moreover, IGF-I levels were measured in both groups. The GH response to GHRH + arginine was significantly lower in PWS patients (GH peak 5.4 +/- 1.3 microg/L; area under the curve (AUC) 311.2 +/- 72.5 microg/L/hr) than obese controls (GH peak 21.0 +/- 4.1 microg/L, P < 0.005; AUC 1241.1 +/- 272.8 microg/L/hr; P < 0.01), as well as IGF-I values (110.5 +/- 16.7 microg/L vs. 242.1 +/- 31 microg/L, P < 0.005). The GHRH + arginine induced GH rise in patients with del15q11-q13 was significantly higher than subjects with UPD15 (GH peak 7.7 +/- 1.7 microg/L vs. 2.7 +/- 1.0 microg/L, P < 0.05; AUC 458.5 +/- 91.0 microg/L/hr vs. 134.4 +/- 46.0 microg/L/hr, P < 0.02). These findings suggested that stimulated GH levels are significantly lower in PWS adults when compared to obese controls and that GH response to GHRH + arginine is different in PWS individuals having separate genetic subtypes.