Growth failure is a recognized feature of the Prader-Willi syndrome (PWS). Despite evidence that hypothalamic dysfunction accompanies the syndrome, the etiology of this growth failure remains controversial because most patients with PWS are obese. In order to contribute to resolution of this controversy, we performed a retrospective analysis of 16 obese and non-obese PWS children. GH deficiency was diagnosed in 12 of the 16 subjects and occurred independently of weight status. All of the non-obese subjects were GH deficient. Of the 4 GH-sufficient children, 2 were moderately obese and 2 were morbidly obese. One of these children had clinical evidence of GH deficiency including a low IGF-1 level. Only one of the children had evidence of GH deficiency and a normal IGF-1 level, a pattern that could be attributable to obesity. We conclude that most short children with PWS have growth hormone deficiency and that this deficiency probably results from hypothalamic dysfunction.