Using primed constant infusions of [14C]urea we assessed the effects in castrate male lambs of insulin-like growth factor (IGF) II infusion on protein metabolism during concurrent IGF-I infusion. A 300 minute infusion of IGF-I at 15 micrograms/kg.hour (n = 4) increased (p less than 0.001) the plasma IGF-I concentration from 72.5 +/- 6.4 ng/ml to 213.6 +/- 17.4 ng/ml and decreased (p less than 0.01) the rate of net protein catabolism (NPC) from 1.48 +/- 0.28 g/kg.day to 1.02 +/- 0.18 g/kg.day. Infusion of IGF-II at a dose of 50 micrograms/kg.hour concurrently with IGF-I at 15 micrograms/kg.hour (n = 4) was associated with a similar rise (p less than 0.01) in plasma IGF-I concentration from 79.4 +/- 4.1 ng/ml to 225.2 +/- 32.8 ng/ml. Plasma IGF-II increased (p less than 0.05) from 350.6 +/- 41.6 ng/ml to 746.7 +/- 165.5 ng/ml over the infusion. Coadministration of IGF-II completely blocked (p less than 0.01) the anabolic effect of IGF-I and the rate of NPC remained unchanged throughout the combined IGF-I and IGF-II infusion at a level comparable to saline infused controls (n = 4). This study suggests that IGF-II may play a physiological role as a circulating modulator of the anabolic effects of IGF-I.