IGF-I promotes growth during postnatal development via both endocrine and autocrine actions. In pcd mice (pcd/pcd), we previously found that IGF-I mRNA expression was decreased in cerebellar Purkinje cells as they underwent apoptosis. To investigate the endocrine function of IGF-I, we examined hepatic IGF-I mRNA by Northern hybridization, circulating IGF-I peptide by radioimmunoassay, and circulating IGFBP by Western ligand blot in pcd mice. At postnatal days (D) 17 and 24, hepatic IGF-I mRNA and circulating IGF-I and IGF-II concentrations were normal in pcd mice. From D45, both hepatic IGF-I mRNA and circulating IGF-I concentrations decreased. The decrease in circulating IGF-I concentrations was accompanied by a simultaneous increase in circulating IGF-II concentrations in both the D45 and adult pcd mice. An early decrease in the circulating IGFBP-3 levels and an increase in the IGFBP-2 levels were observed at D17 and were followed by decreases in both IGFBPs at D45 and in the adult. Therefore, after the cerebellar neurodegeneration, there was an overall decrease in IGF-I gene expression in pcd mice. Our results suggest that the decrease in IGF-I gene expression may contribute to growth deficiency and multiple system degeneration in pcd mice.