We investigated the phenotype and frequency of circulating myeloid dendritic cells (MDC) and plasmacytoid DC (PDC) in 86 multiple sclerosis (MS) patients and 33 healthy controls (HC). The MS group comprised 20 patients with primary progressive MS (PPMS), 20 patients with secondary progressive MS (SPMS), and 46 patients with relapsing-remitting MS (RRMS) [23 treated with interferon-beta (IFN-beta)]. The frequency of circulating MDC and PDC, and the expression of CD83, CD123, CD80, CD86, and CD40 were analyzed by flow cytometry. The percentage of circulating MDC was decreased in patients with SPMS and PPMS. The expression of CD83, CD80, and CD86 was lower in PPMS patients. Treatment with IFN-beta induced the expression of CD123 in PDC and decreased the number of circulating MDC. These results suggest an impaired maturation state of DC in PPMS patients, and a beneficial effect of IFN-beta favouring the survival of PDC and promoting a Th2 environment.