In mice, GH levels rise in response to short-term fasting or starvation (food restriction to 40% of ad libitum intake), similar to that which occurs in humans in response to fasting or anorexia. Recent studies using acyl-ghrelin knockout mice have suggested that the rise in GH during food restriction is essential to support glucose levels. To directly test this hypothesis, adult-onset isolated GH deficient (AOiGHD) mice and their GH-replete littermate controls were provided 40% of ad libitum food intake for 11 d. As previously shown, food restriction increased GH levels in controls, and this response was not observed in AOiGHD mice. In both controls and AOiGHD, food restriction resulted in an initial decline in glucose, which stabilized to 82–85% of ad libitum-fed values by d 2. In addition, loss of lean mass in response to food restriction was not altered by GH status. However, the loss of fat mass and the associated rise in circulating free fatty acids and ketones was blunted in starved AOiGHD mice compared with controls. Taken together, these results suggest a rise of GH during starvation is not required to support glucose levels and muscle mass but may be important in supporting fat mobilization.