The effects of two preparations of highly purified human GH (hGH) on lipid metabolism were studied in the GH-deficient little mouse (50–60 days old). Marked decreases in incorporation of [14C]glucose into fatty acid and in the activity of acetyl-CoA carboxylase in the epididymal fat pads were observed after i.p. injection of hGH at a dose of 1·0μg/g body weight or after continuous infusion of hGH by osmotic minipump. The rate of glucose incorporation into fatty acid decreased from 107·0 ± 27·6 (s.e.m.) to 38·1 ± 19·6 μmol/g tissue per h after a single injection of hGH and from 174·1±28·5 to 56·3±20·3 μmol/g tissue per h after continuous infusion of hGH for 2 days. Activity of the lipogenic enzyme acetyl-CoA carboxylase was also reduced by more than 50% in the epididymal fat pad from hGH-treated mice in comparison with the corresponding control animals. Incubation of isolated fat pads with hGH (0·1 μg/ml) revealed similar inhibitory effects of the hormone on fatty acid synthesis and acetyl-CoA carboxylase activity. No lipolytic effect of hGH was found as determined by the rate of glycerol release from epididymal fat pads of little mice following hormone treatment in vivo or in vitro. The results lend strong support to the conclusion that GH inhibits lipogenesis but has no effect on lipolysis in adipose tissues, and indicate that the physiological role of GH in lipid metabolism is concerned mainly with the regulation of anabolic rather than catabolic processes.