Activin-A, a member of the TGF-beta superfamily, has a variety of important biological functions. Concerning Møs, we demonstrated that MSR which has a key role in disposing of modified LDL is downregulated by activin-A. This leads to a decrease in binding, cell association, and degradation of Ac-LDL, resulting in the inhibition of foam cell formation. Follistatin, presumably by blocking the effect of intrinsic activin-A, upregulates MSR expression, thereby promoting Ac-LDL disposal and foam cell formation. Because both activin-A and MSR are induced during Mø differentiation, these results suggest that MSR expression is suppressed by simultaneous production of activin-A in an autocrine manner. In addition to Møs, activin-A and follistatin exert influences on SMCs and ECs. Examination of in vivo expression of activin-A and follistatin revealed that they are present in various atherosclerotic lesions, including human coronary arteries, suggesting that they are locally produced. Activin-A and follistatin are produced by Møs, SMCs, and ECs in vitro. Thus, the activin-A/follistatin system plays an important role in the development of atherosclerosis.