Although activated human T cells express class II MHC molecules, the biologic significance of this event is not understood. Using two-color flow cytometry, we have analyzed the expression of HLA-DR, -DQ, and -DP isotypes by T cells following activation by allogeneic lymphoblastoid B-cell lines. Within the CD3+ population, transient expression was observed at 1 day following initiation of culture, which preceded a dramatic and sustained increase around 6-7 days. DR expression was always highest, followed by DP and DQ with DP expression usually somewhat higher than DQ. At day 8, three populations were observed consisting of DR+DP+DQ+ (60%), DR+DP+ (69%), and DR+ (75%) T cells. Interestingly, DQ+ or DP+ but DR- T cells were not observed. These patterns of class II isotype expression were similar in CD2+, CD4+, and CD8+ subgroups and suggest that class II molecules are selectively expressed on T cells and may play a role in the regulation of T-cell responses to alloantigens.