Interferon (IFN)-β is among the first-line therapies for multiple sclerosis (MS), however the clinical response varies among individuals, and early identification of responders and non-responders would be of critical importance. Here we show that before treatment circulating lymphocytes of MS patients who will respond to IFN-β have higher mRNA levels for the D1-like dopaminergic receptor (DR) D5 in comparison to cells from those who will not respond. Lymphocyte DR D5 is reduced in MS and IFN-β restores their expression and responsiveness. DR D5 mRNA levels in circulating lymphocytes might represent an early marker of response to IFN-β in MS patients.