Growth hormone (GH) has many metabolic effects, but its mechanism(s) of action are not fully understood. We studied the short-term effects of endogenously produced GH on liver delta 6-desaturase activity and adipose and liver lipid fraction fatty acid composition in transgenic mice. MG101 transgenic mice ages 73-114 d received zinc to activate the ovine GH transgene for 7 d. Nontransgenic littermates, used as controls, also received zinc. Liver lipids were fractionated into phospholipids (PL), cholesteryl esters, and triglycerides (TG), and retroperitoneal adipose fractionated into PL and TG for fatty acid analysis. Liver microsomes were assayed for delta 6-desaturase activity. Animals expressing the ovine growth hormone transgene had a 2.5-fold higher liver delta 6-desaturase activity than controls. Arachidonate and docosahexaenoate were significantly higher in liver PL of GH transgenic animals compared to controls, but both were decreased in adipose PL in the GH animals. We conclude that increased production of GH affects both production and organ distribution of highly unsaturated fatty acids. The changes in arachidonate in various lipid pools following transgene expression may mediate the systemic actions of GH.