Human blood dendritic cells require UV-B radiation (290 to 320 nm) in excess of 1,000 J/m2 to inhibit their stimulation of primary T-cell responses to alloantigen by 60% to 70% or more. The effect is twofold to threefold greater in the allogeneic mixed leukocyte reaction (MLR) than in polyclonal mitogenesis using comparable numbers of dendritic cells and doses of UV-B radiation. UV-B radiation does not significantly alter dendritic cell viability at the doses administered. Dendritic cell expression of important costimulatory ligands, eg, B7/BB1 and ICAM-1/CD54, is reduced in proportion to the dose of UV-B light administered. UV-B irradiated dendritic cells nevertheless initiate stable contacts with primary alloreactive T lymphocytes that are sufficient to prime T-cell responsiveness to interleukin-2 (IL-2). Subsequent proliferation is severely abrogated without supplemental lymphokine, while T-cell alloreactivity is preserved in a secondary response, irrespective of primary exposure to UV-B irradiated dendritic cells.