Several recent reports have described systemic effects associated with insulin-like growth factor-I (IGF-I) infusions in humans, including dizziness, syncope, unconsciousness, bradycardia, and asystole. Eleven healthy volunteers (10 males and 1 female) underwent brachial arterial and deep forearm venous catheterizations to evaluate the effects of an intraarterial infusion of IGF-I on blood flow. Saline was infused into the brachial artery for 1 h, followed by infusions of recombinant human IGF-I (1.25, then 10 micrograms/kg BW.h) over 2 subsequent 90-min periods. Blood flow across the forearm was determined from dye dilution curves after an infusion of indocyanine green dye (20 mg/h) into the proximal arterial port. The rate of saline infusion had no effect on forearm blood flow. Likewise, the low dose arterial IGF-I infusion had no effect on blood flow, even though deep venous IGF-I concentrations increased slightly (127 +/- 37 to 172 +/- 19 ng/mL; P = NS). The 10 micrograms/kg.h infusion rate increased deep venous IGF-I concentrations approximately 4-fold above control values (477 +/- 80 vs. 150 +/- 27 ng/mL, respectively; P < 0.0001), whereas IGF-I concentrations in the peripheral circulation were increased approximately 2-fold (299 +/- 50 ng/mL) above control values (P < 0.0001). Arteriovenous glucose differences, peripheral glucose concentrations, and binding protein-3 concentrations were not influenced by either dose of IGF-I. The 10 micrograms/kg.h dose of IGF-I was associated with a 68% increase in forearm blood flow (71 +/- 8 vs. 42 +/- 6 mL/min, respectively; P < 0.0004). These data suggest that an intravascular infusion of IGF-I results in significant alterations in regional blood flow, which may be related to the observed physiological effects or side-effects associated with its use.