Fifty diabetic patients with chronic painful sensorimotor neuropathy were studied prospectively to clarify the natural history of this condition and the roles of small-fibre damage and concomitant peripheral vascular disease (PVD). Initially, 30 patients had no significant PVD (ankle:brachial Doppler ratio > 1.0). Pain was assessed using a visual analogue scale (0-10 cm), and small-fibre function by thermal limen (TL), heat-pain threshold (HPT), and weighted pinprick threshold (PPT). At follow-up, on average 3.6 years later (range 3.0-4.1), 11 patients had died (6 with PVD) and contact had been lost with 6. Pain scores fell in subjects without PVD (n = 24; median (range), from 4.8 (0.5-10.0) to 2.0 (0.0-9.2) cm, p < 0.001) and also in those with PVD (n = 9; from 5.1 (2.0-8.2) to 2.1 (0.0-8.0) cm, p < 0.05). Seven patients (5 without PVD) became painfree; at presentation, these 7 patients had experienced pain for a shorter period of time. Despite this symptomatic improvement, small-fibre function generally deteriorated in both groups, with significant worsening (p < 0.05) of HPT and PPT in patients without PVD, and in HPT and TL in patients with PVD. Neuropathic pain therefore tends to improve with time and can resolve completely. By contrast, small-fibre function continues to deteriorate, indicating that these peripheral measures do not predict the evolution of painful symptoms. The presence or absence of PVD does not appear to affect the natural history of neuropathic pain or its symptomatology.