Upon activation, tissue residing immature dendritic cells (DC) start to migrate towards the draining lymph node and mature into efficient antigen-presenting cells. During maturation DC loose their capacity to endocytose antigens, change their surface expression of adhesion molecules, chemokine receptors, and costimulatory molecules, and change morphology. We employed 2D-PAGE and mass spectrometry to identify additional differentially expressed proteins in immature and mature DC. Human monocyte-derived DC were matured with LPS and protein expression profiles were compared before and after maturation. One of the proteins differentially expressed between immature and mature DC was identified as the actin-binding protein cofilin. We show here that cofilin is dephosphorylated in response to several maturation stimuli (i.e. CD40 ligand, LPS or a combination of TNF-alpha and prostaglandin E2). Moreover, dephosphorylated cofilin translocated towards the plasma membrane during maturation. Importantly, this correlated with an increase in filamentous actin and the appearance of veils, suggesting a role for cofilin in cytoskeletal rearrangements during maturation.