The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) are present in the nerve endings in the skin and SP is thought to be present at abnormal concentrations in atopic dermatitis (AD) patients. Th1 and Th2 imbalance in AD has been the focus of recent immunological investigations and a preferential Th2 response by atopic cells on stimulation has been proposed. We wished to establish whether neuropeptides acted on T cells to affect their cytokine profile directly, using an accessory cell-independent stimulus (anti-CD3 monoclonal antibody and neuropeptides at several concentrations. We found that interferon (IFN)-gamma and interleukin (IL)-4 release were lower in AD. SP had an enhancing effect on both IFN-gamma and IL-4 at physiological concentrations (10(-10)-10(-6) mol/L) in AD, which was significantly different from controls (P < 0.05). VIP had inhibitory effects over this range in AD and in controls. We conclude that these neuropeptides have a modest effect on T-cell cytokine release and that their action is not cytokine-specific.