In this study we administered aminoguanidine, a relatively selective inducible-nitric oxide synthase (iNOS) inhibitor, in order to study the role of nitric oxide (NO) in LPS-induced decrease in IGF-I and IGFBP-3. Adult male Wistar rats were i.p. injected with LPS (100µg/kg), aminoguanidine (100mg/kg), LPS+ aminoguanidine or saline. Rats were injected at 17:30h and 8:30h the next day and killed 4 hours after the last injection. LPS administration induced an increase in serum concentrations of nitrite/nitrate (P<0.01) and a decrease in serum concentrations of growth hormone (GH) (P<0.05) and IGF-I (P<0.01), as well as in liver IGF-I mRNA levels (P<0.05). The LPS-induced decrease in serum concentrations of IGF-I and liver IGF-I gene expression seems to be secondary to iNOS activation, since aminoguanidine administration prevented the effect of LPS on circulating IGF-I and its gene expression in the liver. In contrast, LPS-induced decrease in serum GH was not prevented by aminoguanidine administration. LPS injection decreased IGFBP-3 circulating levels (P<0.05) and its hepatic gene expression (P<0.01), but endotoxin did not modify the serum IGFBP-3 proteolysis rate. Aminoguanidine administration blocked the inhibitory effect of LPS on both IGFBP-3 serum levels and its hepatic mRNA levels. When aminoguanidine was administered alone, IGFBP-3 serum levels were increased (P<0.05), whereas its hepatic mRNA levels were decreased. This contrast can be explained by the decrease (P<0.05) in serum proteolysis of this binding protein caused by aminoguanidine. These data suggest that iNOS plays an important role in LPS-induced decrease in circulating IGF-I and IGFBP-3, by reducing IGF-I and IGFBP-3 gene expression in the liver.