Eight patients with intensely pruritic lesions of chronic idiopathic prurigo nodularis and three patients with neurodermatitis circumscripta were investigated using the indirect immunofluorescence method. Results showed similarities in epidermal hyperplasia but not in nerve proliferation and neuropeptide immunoreactivity. Increased numbers of calcitonin gene-related peptide (CGRP) and substance P immunoreactive nerve fibre bundles were detected in specimens taken from prurigo nodularis lesions, but no increased immunoreactivity could be seen in specimens taken from patients having neurodermatitis circumscripta compared to normal skin. The neuropeptides, CGRP and substance P, may be responsible for the intense itching of prurigo nodularis lesions.