Psoriasis is a typical hyperproliferative epidermal disease whose aetiopathogenesis is still to be defined. One of the most likely hypotheses is that it has a neurogenic origin correlated with an altered release of some neuropeptides by sensitive cutaneous nerves via antidromic pathways. As there are conflicting reports about the existence of cutaneous nerve alterations in psoriasis, we carried out an immunolocalization study using the protein gene product 9.5 as a marker for neuronal structures observed by confocal laser scanning microscopy in order to determine the pattern of sensory nerves in psoriatic skin. The investigation was carried out on cutaneous biopsies taken from involved (mature and long-established lesions) and uninvolved skin of ten patients with extensive chronic plaque psoriasis. In uninvolved psoriatic skin a significant decrease in epidermal nerve fibres was found, a further decrease was observed in mature lesions and almost a complete lack of epidermal nerve fibres in long-established psoriatic lesions. The reduction in epidermal nerve fibres and the consequent loss of relationship between these nerve structures and the skin immunocompetent cells (antigen-presenting cells, Langerhans cells, keratinocytes) might be a factor of fundamental importance in the self-maintenance of the disease.