In this study, we demonstrate, for the first time, the localization of insulin-like growth factor I (IGF-I) in de novo and restenotic human coronary atherectomy plaques by using immunocytochemical techniques. Smooth muscle cells (SMCs) exhibiting the synthetic phenotype contained a statistically significant higher concentration of IGF-I than SMCs of the contractile phenotype or SMCs from normal coronary arteries. In addition, we provide data to suggest that the long-acting somatostatin analogues octreotide and angiopeptin inhibit IGF-I- and basic fibroblast growth factor (b-FGF)-induced human coronary artery SMC proliferation. Platelet-derived growth factor (PDGF)-stimulated cultures were minimally affected by the addition of octreotide but were significantly inhibited by angiopeptin. All three growth factors stimulated SMC migration in a dose-dependent manner. The somatostatin analogues tested had no effect on growth factor-stimulated SMC migration. Our data suggest that by reducing SMC proliferation, somatostatin analogues may have clinical usefulness in reducing the high incidence of restenosis observed after percutaneous transluminal coronary artery interventions. (Circulation. 1994;89:1511-1517.)