Recently, we have reported three monoclonal antibodies (mAbs) against purified human placental insulin-like growth factor (IGF)-I receptors. These antibodies, in contrast to the well-studied mAb alpha IR-3, stimulate binding of IGF-I and IGF-II to the receptor and DNA synthesis as well [Xiong, et al., Proc. Natl. Acad. Sci. U.S.A. 1992(89), 5356]. Here we describe two additional mAbs, 1H7 and 2C8, against the IGF-I receptor that have characteristics different from either alpha IR-3 or our previously reported mAbs. Both 1H7 and 2C8 bind to the alpha subunit of the IGF-I receptor as determined by immunoblotting. MAb 1H7 inhibited the binding of IGF-I and IGF-II to the IGF-I receptor while 2C8 had no effect on the binding of either ligand to the receptor. When their effects on DNA synthesis were examined using NIH 3T3 cells expressing human IGF-I receptors, 1H7 inhibited basal and IGF-I- or IGF-II-stimulated DNA synthesis whereas 2C8 stimulated basal DNA synthesis but provided no synergism in the presence of IGF-I or IGF-II.