In suspected vasculitic neuropathy, vasculitis is demonstrated in only 30% of superficial peroneal nerve (SPN)/peroneus brevis muscle (PBM) specimens. Pathologic predictors of vasculitis are thus needed for non-diagnostic cases. Immune deposits in epineurial vessels have an established sensitivity but unknown specificity. In this study we assessed specificity using direct immunofluorescence (DIF) in SPN/PBM biopsies for suspected vasculitic neuropathy. Biopsies from 13 patients with vasculitis, 13 without vasculitis, and 6 with diabetic radiculoplexus neuropathy (DRPN) were stained for immunoglobulin G (IgG), IgM, and complement 3 (C3), and analyzed in a blinded manner. Vascular immunoglobulin or C3 deposits occurred in 12 of 13 nerve or muscle biopsies (11 of 13 nerves, 5 of 13 muscles) in vasculitis vs. 1 of 13 (1 of 13 nerves, 0 of 13 muscles) in controls (P = 0.00003). Specificity was 92%. For DRPN, vascular immune deposits occurred in 5 of 6 nerves or muscles (4 of 6 nerves, 1 of 5 muscles), similar to vasculitis but significantly different from controls. Epineurial/perimysial vascular deposits of immunoglobulin/C3 by DIF are a specific marker of vasculitic neuropathy.