Inhibition by anti-HLA Class I monoclonal antibody (mAb) Q6/64 of phytohemagglutinin (PHA)-P-induced peripheral blood mononuclear cell (PMBC) proliferation is associated with a reduction of Tac expression and interleukin 2 (IL-2) secretion. To analyze the mechanism(s) underlying the latter phenomena, the Tac gene and IL-2 gene transcription was analyzed by a nuclear transcription assay. No synthesis of Tac and IL-2 mRNA was detected in PBMC stimulated with PHA-P in the presence of mAb Q6/64. In conjunction with our recently published data, these results indicate that the blocking by anti-HLA Class I mAb of PHA-P-induced PBMC proliferation reflects an inhibitory effect within the signal transduction pathway leading to transcriptional activation of IL-2 and IL-2 receptor genes.