The ability of hormonal therapy to enhance recovery from neonatal malnutrition was assessed in rats. Pups were malnourished via maternal food restriction (60% control intake). On d 16, restricted pups (n = 50) (62% control body wt) were refed until d 20 and were given growth hormone, insulin-like growth factor-I, destripeptide [1,3] insulin-like growth factor-I, or saline (placebo). Refed-placebo pups attained 80% of control body weight by d 20. Growth hormone treatment caused a greater weight gain than refeeding alone (P < or = 0.05). Treatment with insulin-like growth factor-I and destripeptide [1,3] insulin-like growth factor-I did not affect body weight. All three hormones increased spleen and kidney weights (P < or = 0.05) compared with the refed-placebo group, whereas only growth hormone increased muscle weight (P < or = 0.05). Malnourished pups had lower serum insulin-like growth factor-I (P < or = 0.05) and insulin-like growth factor binding protein-3 (P < or = 0.05), and higher serum insulin-like growth factor binding protein-2 (P < or = 0.05) and hepatic insulin-like growth factor binding protein-2 mRNA (P < or = 0.05) than controls. Refeeding increased serum insulin-like growth factor-I compared with restricted pups (P < or = 0.05), and insulin-like growth factor-I treatment caused a further increase in serum insulin-like growth factor-I compared with the refed-placebo group (P < or = 0.05). These results show that growth hormone was moderately effective at increasing body weight gain and muscle growth during recovery from malnutrition.