The effect of fasting on insulin-like growth factor- binding protein-1 (IGFBP-1) expression was examined in the rat. Food deprivation for a period of 24 h resulted in a 9.5 ± 2.0-fold increase in hepatic IGFBP-1 mRNA abundance (P < 0.001). An increase in circulating IGFBP-1 in sera from fasted rats was demonstrated by immunoblotting, and an increased abundance of a 30-kDa IGFBP in sera from fasted rats was apparent when [125I]IGF-I was used in ligand blotting experiments. Refeeding resulted in a prompt decline in hepatic IGFBP- 1 mRNA. Administration of insulin (0.5-4 U, ip) to fasted rats resulted in profound hypoglycemia, but either increased or had no significant effect on hepatic IGFBP-1 mRNA abundance. In contrast, administration of human GH (hGH; 100 μg, ip) resulted in a prompt decline in hepatic IGFBP-1 mRNA, followed by a late rebound in IGFBP-1 mRNA to levels greater than those in fasted controls. Furthermore, hepatic IGFBP-1 mRNA levels were significantly lower in hGH-treated (100 μg every 8 h) fooddeprived rats than in saline-treated food-deprived rats (2.25 ± 1.55- vs. 8.99 ± 3.80-fold increase; P < 0.005). Similar changes were observed when serum IGFBP-1 was quantitated by immunoblotting. The effects of GH could not be explained by secondary hyperinsulinism, since no significant increase in insulin levels was observed in GH-treated rats. From these observations we conclude the enhanced expression of IGFBP-1 in the fooddeprived rat may be a consequence of GH deficiency rather than insulin deficiency. (Endocrinology128: 689–696, 1991)