In order to elucidate the pathogenesis of vasculitis in muscle and nerve a clinicopathological study was performed in 23 patients. The patients could be classified into three groups: I multisystem vasculitis (n = 4); II multisystem disease with vasculitis detectable in nerve, muscle, or both (n = 11); and III localised disease with vasculitis in nerve, muscle, or both (n = 8). Ten of 23 patients had vasculitis in both muscle and nerve biopsies; 6 from groups I and II, and 4 from group III indicating that vasculitis confined to muscle and nerve represents a distinct clinicopathological entity. The neuromuscular manifestations in the 23 patients were sensori-motor polyneuropathy (n = 9), mononeuritis multiplex (n = 6), mononeuropathy (n = 3), proximal myopathy (n = 4), and muscle tenderness without weakness (n = 1). Sensori-motor polyneuropathy was found in 8/11 patients from group II, and mononeuritis multiplex in 5/8 patients from group III. Immunotypic analysis, and immunofluorescence patterns indicate that the pathogenesis of vasculitis in muscle and nerve is heterogeneous and suggest that cell mediated and immune complex mechanisms predominate and may be operative in all three patient groups, with an antibody-mediated humoral mechanism in some patients with paraproteinaemic states (group II).