Epidermal basal cell damage in lichenoid tissue reactions (LTR) is considered to be the result of immunologic injury. In this study, we propose that LTR may be caused by local activation of Ia-reactive T cells. We have established allo-Ia^k-reactive helper T-cell clones and examined their behavior after adoptive transfer. We show that local transfer of 3 allo-Ia^k-reactive helper T-cell clones with different cross-reactivities and functions in vitro can cause delayed type hypersensitivity (DTH) reactions in vivo with antigen specificities identical to those demonstrated in vitro. Clone SK. 1, when injected into appropriate recipients, caused massive dermal infiltrates of neutrophils and mono-nuclear cells. The latter were attracted to the epidermis and induced LTR-like basal cell degeneration which peaked at 72 h. Appropriate recipients were those strains of mice whose spleen cells were able to stimulate SK.1 cells to proliferate in vitro. Two other clones, SK.2.18 and SK.2.16, evoked significant DTH responses in their appropriate recipients, but the massive cellular infiltrates induced by either clone never invaded the epidermis or produced an LTR. The degeneration of epidermal cells caused by SK.1 cells did not correlate with the tested functions of this clone in vitro. The finding that only 1 of the 3 allo-Ia-reactive helper T-cell clones induced epidermotropic cellular infiltrates indicates that the infiltrative pattern of leukocytes in skin may depend on the particular T-cell clone that is activated.