Duplication of the gene for the peripheral myelin protein 22 (PMP22) is the most common cause for Charcot-Marie-Tooth neuropathy type 1a (CMT1A) neuropathy. In early stages of the disease PMP22 is overexpressed in nerve biopsies from CMT1A patients. Recent studies with genetically modified Schwann cells have demonstrated that the altered expression of PMP22 modulates cell growth. Thus we hypothesized that elevated expression of PMP22 at the beginning of the disease might alter Schwann cell differentiation and phenotype. In this study we investigated Schwann cell phenotype in different stages of CMT1A neuropathy using antibodies to established Schwann cell markers. We found a pathological expression of low affinity nerve growth factor receptor (LNGF-R-also referred to in the literature as p75) in numerous Schwann cells of young CMT1A patients with almost normal myelin thickness and very few onion bulbs. During further progression of the disease, when Schwann cells began to form onion bulbs, we observed an intense LNGF-R immunoreactivity in all layers of the onion bulbs. In the most advanced stages of the disease, characterized by massive onion bulb formation, no LNGF-R immunoreactivity was shown. In age-matched control nerves LNGF-R staining was barely detectable. Furthermore, onion bulbs seen in patients with chronic idiopathic polyneuropathy (CIDP) were always negative for LNGF-R. In addition, at all CMT1A disease stages analysed, LNGF-R-positive Schwann cells were glial fibrillary acidic protein (GFAP) negative. Immunostaining with an antibody to the proliferation marker, proliferating cellular nuclear antigen (PCNA) indicated Schwann cell proliferation when onion bulb formation was well developed. In conclusion, we describe a disease stage-dependent altered Schwann cell phenotype in CMT1A neuropathy, which could be a direct consequence of the PMP22 overexpression on Schwann cell growth behaviour or, less likely, a secondary phenomenon related to myelin loss.