The actions and interactions of exogenous insulin-like growth factor-I (IGF-I) and bovine GH (bGH) on protein metabolism were investigated in vivo using Snell dwarf mice. Mice were administered a daily dose of 1.5 or 20 micrograms bGH in the presence or absence of 20 micrograms IGF-I. IGF-I and GH stimulated significant increases in whole body weight gain. Serum IGF-I concentrations increased dramatically in mice administered IGF-I, but more modestly in GH-treated mice. However, greater increases in tissue IGF-I content were observed for GH- than for IGF-treated mice, implying that GH exerted its anabolic actions by local IGF-I synthesis. Skeletal muscle (combined gastrocnemius plus plantaris) weight was significantly increased in GH-treated mice and tended to increase in IGF-treated mice. Muscle protein synthesis was stimulated by about 50% in mice treated with IGF-I alone and the lower dose of GH and by over 100% in the group treated with 20 micrograms/day GH compared with that in saline-treated mice; further additive increases in synthesis rates were observed for mice administered both IGF-I and GH. In all cases, this stimulation was due to both increased RNA content and efficiency of protein synthesis, expressed as grams of protein synthesized per g RNA/day. Liver weight and protein synthetic rate were increased by as much as 25% and 34%, respectively, in GH-treated mice, but IGF-I inhibited hepatic protein metabolism, tending to decrease synthesis rates and inducing a decrease in the efficiency of protein synthesis. Thus, IGF-I and GH have specific and differential effects on tissue protein metabolism in this model.