The plasma concentration and liver mRNA content of IGF-I are regulated by the quantity and quality of dietary proteins. To determine whether the synthesis of IGF-binding proteins (BPs) is also affected by protein nutrition, we assessed plasma concentration, tissue mRNA content and liver transcription rate of each BP after rats were fed either a 12% casein or a protein-free diet for 1 week. Protein deprivation reduced the plasma concentration of IGFBP-3 and IGFBP-4 and increased that of IGFBP-1 and IGFBP-2. The mRNA content in tissues and liver transcription rates of IGFBP-3 and IGFBP-4 did not change in response to protein deprivation although their plasma concentrations decreased. The increased plasma IGFBP-1 and IGFBP-2 concentrations were explained by the increased mRNA content and transcription rate of their genes in the liver. Although IGFBP-1 mRNA was increased by protein deprivation not only in liver but also in kidney, IGFBP-2 mRNA was increased only in liver and did not increase in any other tissue examined. In addition, the liver mRNA content of the acid-labile subunit, which can form a ternary complex with IGFs and IGFBP-3, was not affected by protein deprivation. These results show that tissue-specific synthesis of each BP is regulated in a distinct way in response to protein deprivation.