Adults with atopic dermatitis (AD), with respiratory atopy only and healthy non-atopic controls were given intradermal injections of substance P (SP), neurokinin A (NKA), neurotensin (NT), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and histamine into the normal-appearing skin on the back. The weal and flare responses were evaluated after 3, 5 and 15 min and the areas calculated using an automatic image analyser. With the three different concentrations used (1,3 and 30 pmols) a statistically significant (P < 0·05) reduction in both the weal and flare response to SP, NKA, NT and histamine and a reduced flare to CGRP was observed only in AD patients. Among those with AD there was no uniformity of response to the individual neuropeptide and in general the more severely affected showed a lower reactivity. Dose-response relationships were evaluated for SP and NT (10–320 pmols) in AD and healthy controls. In AD dose-response curves and time-course relationships were similar to controls, but at significantly reduced levels. The itch response to the neuropeptides and histamine was not different in atopics and controls. We suggest that this hyporesponsiveness in AD is the result of natural tachyphylaxis of the target structures (mast cells and blood vessels) and possibly due to a higher availability of neuropeptides in the skin or to a primary abnormal sensitivity of the blood vessels and mast cells to these peptides.