Abstract Despite the plethora of information on immune mechanisms derived from studies of autoimmune experimental encephalomyelitis (EAE), the animal model of multiple sclerosis, little information is available in terms of the kinetics of presentation of myelin antigens by APCs in the CNS. The purpose of this study was to show at which time points and by which APCs myelin antigen (MBP, MOG, PLP) was acquired and presented after induction of EAE. To address this issue, mice were immunized with MOG 35-55 peptide and injected with pertussis toxin on day 0 and 2 and followed for disease. Representative mice were sacrificed every day over forty days and brain tissue was recovered for immunofluorescence analysis. Immunofluorescence and confocal microscopy was used to determine expression of APC cell surface markers and myelin antigens. The results show that T cells or dendritic cells (DC) were rare (<1 cell per 500 fields) in non-immunized mice. In contrast, numbers of CD4+ T cells in immunized mice began to increase at day 3, and numbers of DCs showed a notable increase around day 9. Myelin laden DCs appeared between day 11 and 13. Inflammatory infiltrates peaked between days 15 to day 20, coinciding with peak EAE scores. In conclusion, our data suggest that infiltration of CD4+ T cells precedes substantial uptake and presentation of myelin antigens by CNS APCs, which could have important treatment implications.