This report describes the purification, sequences, and activities of insulin-like growth factors (IGFs) from adult and fetal sheep plasma. IGF-1 from adult sheep is identical to human and bovine IGF-I, except for substitution in the sheep of Ala at residue 66 for Pro in the human and bovine polypeptides. IGF-II from adult sheep differs from bovine IGF-II also by a single amino acid, with residue 62 being Ala in ovine and Thr in bovine IGF-2. The first 10 amino-terminal residues of fetal sheep plasma IGF-I and 92% of the amino acids of fetal IGF-II were identified and found to be the same as those of the corresponding IGFs isolated from adult sheep. Ovine IGF-I was virtually equipotent with human IGF-I in growth-related bioassays and in a RIA for human and bovine IGF-I and inhibited the binding of radiolabeled human IGF-I to type I IGF receptors and to a pure IGF-binding protein. Ovine and bovine IGF-II were also found to be similar to each other in biological and immunochemical activities, and in their binding to type I and II IGF receptors and IGF-binding protein. As observed with human and bovine IGF-I and IGF-II, ovine IGF-I bound slightly better to type I IGF receptors than ovine IGF-II, but bound very poorly to type II IGF receptors. This study shows that IGFs from sheep are very similar to those of human and bovine in structure and activity and defines sensitive radioligand assays specific for ovine IGF-I and ovine IGF-II.