We investigated brain samples of patients with multiple sclerosis (MS) and controls with immunohistochemistry using monoclonal antibodies (MoAbs) against canine distemper virus (CDV) and measles virus (MV) proteins. All stained negative except for MoAb F3-5, which recognises a conserved epitope on the fusion protein of morbilliviruses. F3-5 immunostaining was found in 8/9 MS plaques and 2/5 herpes simplex virus encephalitis brain samples, but not in six controls or four patients with ischaemic stroke. Using RT-PCR we found no evidence for the presence of MV in MS plaques. The F3-5 epitope may represent a protein that is upregulated during inflammation or point to a yet unrecognised morbillivirus in the human central nervous system that might be implicated in MS pathogenesis.