To avoid unsuspected and unwanted consequences of excess hapten during epicutaneous sensitization, optimal sensitizing doses of dinitrofluorobenzene (DNFB) were determined for several ultraviolet B radiation (UVB) - resistant and UVB-susceptible strains of mice. Using these doses of hapten applied epicutaneously or injected intracutaneously into normal or UVB-exposed body wall skin, it was determined that four consecutive daily exposures to UVB prevented contact hypersensitivity induction in all mice when optimal sensitizing doses of DNFB were applied epicutaneously. By contrast, UVB-resistant, but not UVB-susceptible, mice developed contact hypersensitivity when an optimal sensitizing dose of DNFB was injected intracutaneously into UVB-irradiated skin. Moreover, whereas UVB-susceptible mice failed to develop contact hypersensitivity when an optimal sensitizing dose of DNFB was painted on skin exposed to a single dose of UVB, UVB-resistant mice did develop contact hypersensitivity under similar circumstances. Based on these results, it is concluded that 1) conventional doses of epicutaneously applied haptens induce contact hypersensitivity with the aid of antigen-presenting cells derived from both the epidermis and the dermis, 2) the phenomenon of UVB susceptibility is mediated by cells and molecules within the dermis when conventional doses of hapten and UVB radiation are employed, and 3) UVB susceptibility is mediated by cells and molecules within the epidermis when optimal sensitizing doses of hapten and a single exposure to UVB are employed.