Small cell lung cancer (SCLC) cell lines were examined for the presence of insulin-like growth factor I-related protein (IGF-I) in cell pellets and culture media. IGF-I immunoreactivity was detected in 11/14 pellets, ranging from 12 to 76 mIU/mg soluble protein. The IGF-I levels in the cell pellets showed a correlation to the corresponding culture media. IGF-I binding sites were found in all tested cell lines. The maximum binding (Bmax) ranged from 131 to 1230 fmol/mg protein and the dissociation constant (KD) from 0.89 to 5.21 nM. The incorporation of [3H]thymidine in the presence of recombinant human IGF-I resulted in a clearly increased DNA synthesis in two of seven cell lines. Thus, IGF-I may be an important growth factor in SCLC.