Polychlorinated biphenyls (PCBs) induce apoptotic cell death of HL-60 cells. In the present study, we examined the possible involvement of protein kinase C (PKC) in PCB-induced apoptosis of HL-60 cells. Treatment of cells with phorbol 12-myristate 13-acetate (PMA), an activator of PKC, suppressed DNA fragmentation induced by PCBs in HL-60 cells. Treatment with another active phorbol ester, phorbol-12,13-dibutyrate (PDBu), also suppressed PCB-induced DNA fragmentation, whereas 4alpha-phorbol-12,13-didecanoate (4alphaPDD), an inactive phorbol ester, did not affect PCB-induced apoptosis of HL-60 cell. Moreover, 1-oleoyl-2-acetyl-sn-glycerol (OAG), an activator of PKC that is not a phorbol ester, also suppressed PCB-induced DNA fragmentation. However, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of PKC, increased DNA fragmentation induced by PCBs. These results demonstrate that the activation of PKC is responsible for the suppression of PCB-induced apoptosis of HL-60 cells. Furthermore, inhibition of PKC promotes DNA fragmentation of HL-60 cells treated with PCBs, thereby suggesting the involvement of PKC activity in PCB-induced apoptosis of HL-60 cells.