Three mouse lines with altered growth hormone (GH) signaling were used to study GH's role in adiposity. Dwarf GH receptor knockout mice (GHR -/-) and bovine GH antagonist expressing mice (GHA) had an increased percent body fat with most of the excess fat mass accumulating in the subcutaneous region. Giant bovine GH expressing mice (bGH) had a reduced percent body fat. Only GHA mice consumed significantly more food per body weight. Serum leptin levels were significantly increased in GHA mice and decreased in bGH mice but unchanged in the GHR -/- mice. Interestingly, serum adiponectin levels were significantly increased in the GHR -/- and GHA lines but decreased in bGH mice. These data suggest that suppression or absence of GH action and enhanced GH action indeed have opposite metabolic effects in terms of adiposity. Interestingly, adiponectin levels were positively correlated with previously reported insulin sensitivity of these mice, but also positively correlated with adiposity, which is contrary to findings in other mouse models. Thus, adiponectin levels were negatively correlated with GH function suggesting a role for adiponectin in GH-induced insulin resistance.