IFNalpha is an immunostimulatory cytokine involved in the development of autoimmunity. Atorvastatin, a cholesterol-lowering drug, also possess immunomodulatory effects, being able to downregulate IFNgamma-induced MHC-II expression. In this study we evaluated the role of IFNalpha in monocyte differentiation to antigen-presenting cells (APCs) and the effect of atorvastatin during this process. Results showed that IFNalpha-treated monocytes differentiated into dendritic-like cells (IFNalpha-DLCs) characterized by a CD86(high), CD1a(low), MHC-II(high) and CD14(low) expression, consistent with the phenotype of mature DCs and with similar ability to uptake antigens and induce T cell responses to mature IL-4/GM-CSF-DCs. Interestingly enough, the presence of atorvastatin did not inhibit IFNalpha-induced HLA-DR expression, although this drug markedly reduced the ability of IFNalpha-DLCs to induce T cell responses. These results confirm the immunostimulatory role of IFNalpha by promoting the generation of APCs and provide new clinical applications of statins as modulators of autoimmune responses in patients with high pathological or pharmacological IFNalpha levels.