Background. Vessel injury provokes the release of proinflammatory cytokines and growth factors that influence vascular smooth muscle cell (VSMC) proliferation and migration. Produced by T lymphocytes, interleukin- 10 (IL-10) and interferon-γ (IFN-γ) both have immunoregulatory functions and act on Similar receptors, designated class II cytokine receptors. We hypothesized that the class II cytokine receptor participates in vascular remodeling by inhibiting VSMC proliferation. The purposes of this study were to determine the influence of class II cytokine receptor stimulation on (1) unstimulated, (2) cytokine-stimulated, and (3) growth factor-stimulated VSMC proliferation. Methods. Human aortic VSMCs were isolated and cultured. VSMCs were treated with IL-10 or IFN with or without tumor necrosis factor-α (TNF- α) or basic fibroblast growth factor (FGF). Proliferation was quantified by colormetric assay. Results. Compared to control, both TNF and FGF stimulated concentration-dependent VSMC proliferation (P < .005). IL-10 and IFN alone had no effect on unstimulated cell growth. With TNF or FGF stimulation, both IL-10, at a dose as low as 10 fg/mL, and IFN, at a dose as low as 1.0 U/mL, inhibited cell growth (P <. 001). Conclusions. The class II cytokine receptor ligands, IL-10 and IFN, inhibit cytokine- (TNF) and growth factor- (FGF) induced VSMC proliferation. The class II cytokine receptor may provide a novel therapeutic target in regulating vessel wall remodeling after vascular injury.