Myeloid and plasmacytoid dendritic cells (DC) are present in cerebrospinal fluid (CSF) in non-inflammatory neurological diseases (NIND) and elevated in clinically definite multiple sclerosis (MS) and in early MS - acute monosymptomatic optic neuritis (ON). Here, we show that expression of CCR5, a chemokine receptor for regulated on activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein (MIP)-1alpha/beta, is elevated on blood myeloid (CD11c+) DC in MS and ON compared to non-inflammatory controls. In contrast, expression of CXCR4, a receptor for stromal cell-derived factor (SDF)-1alpha, is similar in all groups. Blood myeloid DC from MS patients respond chemotactically to RANTES and MIP-1beta, which are expessed in MS lesions. In active MS and ON, expression of CCR5 by myeloid DC in blood correlates with numbers of these cells in CSF. Thus, elevation of CCR5 may contribute to recruitment of myeloid DC to CSF in MS and ON. Recruitment of plasmacytoid DC to CSF appears to be CCR5-independent.