We have developed a method for large scale purification of insulin-like growth factor I (IGF-I, mecasermin) from a fused protein in which IGF-I is linked to a portion of interferon-gamma through a methionine residue. Although IGF-I itself carries a methionine residue at the 59th position, the fused protein was selectively cleaved with cyanogen bromide at the methionine residue at the linkage site by optimization of the degradation conditions and converted to reduced IGF-I with high yield. We also found that the efficiency of renaturation of the reduced IGF-I to the native conformation was greatly increased in the presence of 1.0 M guanidine-HCl and 30(v/v)% ethanol. The renatured IGF-I was purified using cation-exchange chromatography and reversed-phase HPLC to give recombinant IGF-I of more than 97% purity.