OBJECTIVE: Our objective was to examine the scores and reproducibility of a 47 item Quality Of Life questionnaire (Norfolk QOL) previously constructed using the Delphi method to inventory neuropathy subscales: symptoms, involvement of small, large, autonomic nerve fibers, and activities of daily living (ADL). METHODS: We studied 242 subjects comprising three groups: 75 healthy control (C); 86 diabetic control without neuropathy (DC); and 81 diabetic patients with peripheral neuropathy (DN). The questionnaire was administered to all three groups and repeated at 1-3 month intervals to determine scores, reliability and reproducibility. One-way analysis of variance (ANOVA) and Tukey-Kramer post hoc (=0.05) tests were used to compare the different groups and Cronbach alpha coefficients of internal consistency and intra-class correlation coefficients (ICC) to test reproducibility. RESULTS: Overall the DN group (39.8 ± 3.3) scored 3-4 fold higher than DC (12.8 ± 1.5) and 6-10 fold higher than C (5.8 ± 1.0). Scores for each subscale were <1-5.1 in C and 1.3-11.2 in DC whereas DN scores were: autonomic 4.0 ± 0.3; small fiber 8.3 ± 0.7; large fiber 11.3 ± 1.1 and ADL 31.6 ± 2.8 (p<0.05 for all). DC scored higher than C because of urinary problems in females and erectile dysfunction in non-neuropathic males. ADLs were worse in DC because of diabetes and its complications other than neuropathy accounting for the feeling of accomplishing less. All items met the requirements of a Cronbach alpha coefficient of internal consistency >0.5 and ICC r>0.9. CONCLUSIONS: The Norfolk QOL domains and individual items are reproducible in all groups. This instrument is sensitive and specific for the different features of diabetic neuropathy and has the capacity for providing non-invasive clinical guidelines for assessing disease impact and for evaluating responses to treatment.