Dendritic cells (DC) are currently employed as cellular vaccines in clinical trials of tumor immunotherapy. In most trials, peptide epitopes derived from tumor antigens are being exogenously loaded onto human DC for binding to MHC class I molecules. While this is a convenient method, it suffers from the drawback that the persistence of class I/peptide complexes on the cell surface is in the order of a few hours. This drawback limits the success of vaccination. We have investigated biodegradable poly(D,L-lactide-co-glycolide) microspheres (PLGA-MS) as delivery tools for antigen loading of human monocyte-derived DC (hMoDC). Immature hMoDC readily take up PLGA-MS and present epitopes from encapsulated proteins or peptides both on MHC class I and class II. Interestingly, antigen presentation by hMoDC was markedly prolonged when hMoDC were charged with PLGA-MS-encapsulated as opposed to soluble antigens. The properties of hMoDC with respect to migration, cytokine secretion, survival and allostimulation were not adversely affected by the uptake of PLGA-MS. In this article, we will review the properties of PLGA-MS as an adjuvant and summarize recent data on their potential for antigen delivery to dendritic cells.