Sixteen patients with essential mixed cryoglobulinemia were studied and followed up clinically and electrophysiologically for 4.2 years. Peripheral neuropathy was diagnosed in seven cases. Five of these patients had distal symmetrical sensorimotor polyneuropathy. Nerve conduction velocities were normal and therefore indicative of pure axonal neuropathy. Sural nerve biopsy showed moderate loss of myelinated axons in two patients and severe loss in one. This patient also had necrotizing arteritis. The remaining two had both clinical and electrophysiologic signs of overlapping mononeuritis multiplex with severe denervation in the territory of the involved nerves, but normal conduction velocities. Sural nerve biopsy in one of these two patients showed marked loss of myelinated fibers and signs of vasculitis. Two types of neuropathy were noted: (1) a mild distal neuropathy with relatively minor neurologic deficit, probably due to vasa nervorum microcirculation occlusion caused by intravascular deposits of cryoglobulins and (2) a severe distal symmetrical sensorimotor neuropathy or overlapping mononeuritis multiplex, associated with necrotizing vasculitis.