BACKGROUND The minimally invasive method of skin biopsy with intraepidermal nerve fiber (IENF) counts may be used to analyze nerve regeneration in pancreas transplant (PTx) recipients. We assessed IENF counts as a database for long-term follow-up of diabetic neuropathy. METHODS Skin biopsies were performed using a 3-mm punch from lower thigh and upper calf areas of 16 (13 pancreas/kidney, 3 pancreas alone) PTx patients (mean +/- SD: age, 45+/-8 years; type 1 diabetes duration, 27 +/- 8 years) at 1 month posttransplant. Ten healthy gender- and age-matched controls (C) were also examined. After fixation and freezing, 40-microm sections were stained using rabbit polyclonal antibody to the panaxonal marker PGP 9.5 followed by mouse antirabbit IgG antibody conjugated with rhodamine. Samples were imaged with a digital camera, mounted on a microscope, and equipped for fluorescence. The average number of IENF per millimeter length of epidermis was derived. Clinical neuropathy was assessed by foot vibration perception thresholds (VPT) with a biothesiometer (normal values < mean + 2 SD of C). RESULTS Significantly lower IENF densities were found in skin biopsies from PTx (PTx vs C: thigh, 0.74 +/- 0.88 vs 9.74 +/- 2.41 IENF/mm; calf, 0.34 +/- 0.91 vs 7.66 +/- 3.16 IENF/mm; P < .001). IENF were totally absent from the thigh and calf samples of 7 and 12 PTxs, respectively. Clinical neuropathy (VPT > 21 V) was present in all but one PTx. CONCLUSIONS Severe intraepidermal nerve fiber depletion is present in the lower limb area of pancreas transplant recipients with neuropathy. Long-term follow-up would probably be necessary to assess the possibility of posttransplant nerve fiber regeneration.