We compared the sural nerves from patients with AIDS; four with the painful peripheral neuropathy (PPN), three patients with non-painful distal symmetrical peripheral neuropathy (DSPN), one without clinical peripheral nerve involvement and two human immunodeficiency virus negative controls. Fibre diameter distributions showed a slight reduction in larger fibres in all patients with AIDS compared with controls. No significant difference was found in the relative frequency distribution of the lamellae counts between any of the groups. The relative frequency distribution of axonal area of myelinated fibres did not differ between controls, non-painful DSPN or the patient without peripheral nerve involvement; however, all patients with PPN showed marked reduction in the number of axons of myelinated fibres of larger area which was significant when compared to each patient from the other groups (P less than 0.0001). This indicates that the reduction in larger fibres in PPN is mostly due to axonal atrophy rather than selective fibre loss. Axonal atrophy is associated with painful peripheral neuropathy in AIDS but not with those without pain. The possible role of axonal atrophy as a pathological substrate for pain is discussed.