Activin-A has a mitogenic effect on vascular smooth muscle cells (SMCs) and is produced by monocyte/macrophage lineage cells. Here, we studied the expression of follistatin, an activin-binding protein, in both A10 cells, a rat aortic SMC line, and vascular SMCs derived from adult rat aorta. Follistatin mRNA was detected in these cells by Northern blot analysis. Ligand blot and immunoblot analyses demonstrated that follistatin was produced in the conditioned medium at a higher level by A10 cells than by SMCs. Furthermore, immunostaining and in situ hybridization of the arteriosclerotic lesions showed that follistatin was highly expressed in the diseased artery, where abnormal proliferation of SMCs occurred. We suggest that follistatin is produced by vascular SMCs and is involved in the course of atherogenesis.