The phenomenon of antigenic modulation was studied in the histiocytic lymphoma line U937. A redistribution of cell surface HLA antigen after incubation of U937 cells with the monomorphic anti-HLA class I monoclonal antibody W6/32 was demonstrated by immunofluorescence analysis. As assessed by hybridization of RNA obtained from W6/32-treated U937 cells with a probe corresponding to the alpha 3 domain of HLA Cw3, prolonged W6/32 incubation (24 to 72 hours) induced a decrease in HLA class I transcript abundance. This decrease was about 25% as compared with untreated control cells. These data indicate that W6/32 incubation can induce changes in HLA class I gene expression not only at the antigenic but also at the transcriptional level. Possible implications for the molecular basis of antigenic modulation are discussed.