Insulin-like growth factor-II (IGF-II) is a major factor produced by skeletal tissues. To evaluate endocrine effects of IGF-II on bone growth, we measured skeletal dimensions of 12-week-old transgenic mice harbouring fusion genes where a human IGF-II cDNA is transcriptionally controlled by rat phospheonolpyruvate carboxykinase (PEPCK) promoter sequences. Transgene expression in liver, kidney and intestine resulted in circulating IGF-II levels in transgenic mice which were 2-3-fold higher than in controls. Serum IGF-I concentrations of transgenic mice were lower than in controls. Body weight was not influenced by the expression of the IGF-II transgene. Only 1 out of 5 measurements taken from the radius was significantly affected by the presence of the transgene, while in 60 measurements taken from eight other bones there was no difference between transgenic mice and controls. Furthermore, serum levels of calcium and phosphate as well as alkaline phosphatase activity were not significantly altered in PEPCK-IGF-II transgenic mice. Our findings demonstrate that moderately increased levels of circulating IGF-II do not cause major changes in skeletal growth and turnover in mice. This may be due to a lack of activity of circulating IGF-II on bone growth or to physiological consequences of elevated IGF-II, like a reduction of circulating IGF-I or an increase in IGF binding proteins.