Among 54 patients with mixed cryoglobulinemia a peripheral neuropathy was demonstrated in 23 patients (42.6%). Five patients had a secondary form while the majority (18) had essential cryoglobulinemia. The immunoglobulin components were polyclonal in 5 cases, only present in trace amounts in 5 and of type II in 13 patients. Fifteen patients had symptoms of polyneuropathy, but in 18 cases the symptomatology had symmetrical features and in two cases asymmetrical characteristics. In 8 patients a mono-polyneuropathy was observed. The most significant electrophysiological finding was the decreased amplitude of the sensory action potential of the sural nerve, which we observed in 95% of the instances, whereas a decreased sensory conduction velocity was seen in 8/23 cases only. A biopsy of the sural nerve, performed in eleven cases, always showed abnormal epi- and endoneurial vessels. Epineurial vessel vasculitis was found in 4 cases and fibrous thickening of the vessel wall in two cases. Endothelial swelling of the endoneurial vessels was observed in 7 patients and luminal obliteration in 3 samples. Axonal degeneration demonstrated in 7 of the 11 processed sample tissues was the main pathological finding. Signs of de/remyelination were associated in 3 cases, and were the dominant lesions in a single specimen. The simultaneous biopsy of the peroneus brevis muscle showed signs of denervation in all samples, vasculitis in 7 cases and deposits of filaments plus annular bodies of the vessel wall in 2 samples. All these data support the hypothesis that ischaemic damage may be the final common pathway of the majority of peripheral neuropathies in mixed cryoglobulinemia patients.