Systemic growth hormone and locally administered insulin-like growth factor-I have been shown in a number of studies to improve the breaking strength of incisional wounds, especially in compromised animals. The objective of the present study was to compare these two agents when administered subcutaneously distant from an incisional wound site in pigs, as well as to examine effects of a combination growth hormone/insulin-like growth factor treatment. Growth hormone was shown to increase wound breaking strength in two experiments, whereas insulin-like growth factor-I or a more potent analog had no effect. Moreover, breaking strength was only minimally improved above the vehicle groups by the combination of growth hormone and insulin-like growth factor-I. These effects could not be explained by changes in plasma insulin-like growth factor-I concentrations which were highest in the combination groups, nor by plasma insulin-like growth factor binding protein-3 which was raised equally whenever growth hormone was administered. We conclude that systemic growth hormone but not insulin-like growth factor-I improves wound strength in normal pigs, whereas insulin-like growth factor-I reduces the magnitude of the growth hormone effect by an unknown mechanism.