A lack of trophic support may lead to degeneration of adult nerve cells. Several growth factors, including insulin-like growth factor I (IGF-I), control the survival of spinal motor neurons during development as well as after experimental injury. These neurons are selectively affected in patients with amyotrophic lateral sclerosis (ALS). Thus, we analyzes whether reduced levels of circulating IGF-I may be present in this disease. Significant increases were found in three of four of the main circulating IGF-binding proteins in ALS patients, whereas serum IGF-I and insulin levels were significantly reduced. On the contrary, multiple sclerosis patients did not show any significant change in the IGF-I trophic system even though oligodendrocytes are known targets of the trophic action of IGF-I. These results suggest an involvement of the peripheral IGF-I trophic system in ALS.