Interleukin-11 (IL-11) is a growth factor for megakaryocytes, osteoclasts, and intestinal mucosa. IL-11 is also an anti-inflammatory agent mediating many of its effects by inhibition of the transcriptional activator nuclear factor kappa-B (NFB). The purposes of this study were to examine the effects of IL-11 on human vascular smooth muscle cell (VSMC) proliferation and NFB activity. VSMC were cultured from human transplant donor aortas, stimulated with basic fibroblastic growth factor (bFGF), and treated with IL-11. VSMC stimulated with bFGF demonstrated an increase in cell number by direct cell counting and mitochondrial activity. IL-11 caused a concentration-dependent decrease in bFGF-induced VSMC proliferation. Furthermore, IL-11 attenuated bFGF-induced increases in cytoplasmic and intranuclear unbound NFB p65. Similarly, IL-11 attenuated VSMC expression of two NFB-dependent cytokines, interleukin-8 and -6. Stimulated VSMC did not secrete IL-11, suggesting endogenous IL-11 did not account for our observations. In conclusion, IL-11 inhibits human VSMC proliferation in vitro and is associated with suppression of NFB.