In the majority of patients, allergic nickel contact dermatitis is associated with a proliferative response of peripheral blood T lymphocytes to nickel sulfate. Optimal proliferation was found in a concentration range of 1-2 X 10(-4) M nickel sulfate. Nickel-specific response of purified peripheral blood T cells requires the presence of antigen-presenting cells (APC). Both peripheral blood monocytes and skin-derived epidermal cells could function as APC, but epidermal cells were shown to be more potent than monocytes. By testing FcR+ monocytes and FcR- circulating dendritic cells for their antigen-presenting capacities, it was found that the critical APC within the fraction of monocytes is the circulating dendritic cell. Testing highly purified T6+ (CD 1) skin-specific dendritic cells (Langerhans cells, LC) and T6- epidermal cells as APC, the critical APC within the fraction of epidermal cells appeared to be the LC. The crucial role of LC was stressed in experiments using T cells from patients exhibiting a positive patch test to nickel but a low or absent proliferative response to nickel by unpurified peripheral blood cells. Whereas addition of peripheral blood APC was ineffective, addition of LC to purified peripheral T cells was shown to overcome this low responsiveness to nickel. These results indicate the crucial role of dendritic APC subsets in nickel-specific T-cell proliferation.