We have previously demonstrated that in vitro exposure of antigen-presenting cells to UVB radiation inhibits their ability to activate T cells through selective effects on the expression of the adhesion molecule ICAM-1 (intercellular adhesion molecule-1). Intercellular adhesion molecule-1 is an important costimulatory molecule provided by antigen-presenting cells for T-cell activation. Using human peripheral blood monocytes and the U937 human monocytoid cell line as model antigen-presenting cells, we investigated the effect of UV radiation on the mRNA steady-state levels for human ICAM-1 by northern blot analysis and relative transcription rates of ICAM-1-specific mRNA by nuclear run-on assay (NRO). Northern blot analysis demonstrated a decreased level of ICAM-1 mRNA at 4 h postradiation relative to glyceraldehyde-3-dehydrogenase mRNA. The NRO analysis demonstrated a greater than 35% decrease of newly synthesized specific mRNA at 4 h postirradiation. The results demonstrate a transcriptionally based mechanism for the diminution of both mRNA and translatable mRNA specific for ICAM-1 regulation in UV-treated antigen-presenting cells.