Natural blood-borne antigen-presenting cells (APCs) were tested for their ability to augment antigen presentation for SIV vaccines. Fibrocytes and monocyte-derived dendritic cells (DCs) were isolated from multiple Macaca fascicularis. Macaque fibrocytes displayed the characteristic cellular morphology and stained positive for CD34 and collagen, as observed in human and murine fibrocytes. Macaque DCs were generated from monocytes by culturing in granulocyte-macrophage colony stimulating factor and interleukin-4 (IL-4). Two days after maturation, cells were enriched for the DC marker CD83. Fibrocytes and DCs were each transfected with green fluorescence protein expression plasmids or DNA expression vectors encoding all of the SIVmne structural and regulatory genes. Autologous DCs were re-infused into macaques subcutaneously (sc) following transfection; mixing with recombinant SIV antigens or inactivated whole SIV in vitro; or mock-treatment. Autologous monocyte-derived DCs pulsed with whole inactivated SIV were re-infused and elicited cellular and/or humoral responses in vivo in eight of ten vaccinated macaques.