Twenty-four patients with clinically defined multiple sclerosis were prospectively studied with the aim of establishing the frequency of retinal periphlebitis. In three cases (12.5%) retinal periphlebitis was observed. None of the patients with multiple sclerosis and retinal periphlebitis presented a severe form or progressive course of the disease; however, in one patient it caused complete unilateral amaurosis. Aggressive immunosuppressive treatment was effective in one case. Given the absence of myelin in the retina, the presence of retinal periphlebitis suggests the existence of a vascular mechanism in the pathogenesis of multiple sclerosis.