Methylsulphonyl polychlorinated biphenyls (MSF-PCBs) have already contaminated at relatively high concentration in the lungs and blood of Yusho patients and healthy Japanese people. Therefore, we should give due attention to their biological and toxicological effects to man. In this study, in order to evaluate S-dependent genotoxicity of five MSF-PCB congeners, namely, 3-MSF-4,5,3',4'-tetrachlorobiphenyl (TCB), 3-MSF-4,5,2',3'-TCB, 3-MSF-2,5,2',4',5'-pentachlorobiphenyl (PenCB), 4-MSF-2,5,2',3',4'-PenCB and 4-MSF-2,5,2',3',5',6'-hexachlorobiphenyl (HCB), we have examined their effects on the induction of sister chromatid exchanges (SCEs), which has been frequently used to estimate the dose of S-dependent clastogens, in cultured human lymphocytes in the absence or presence of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,4,5,3',4'-pentachlorobiphenyl (Co-PenCB) and the following results were obtained. 1) 4 x 10(-5)M, 7,8-benzoflavone (ANF) and two of the five MSF-PCB congeners, namely, 3-MSF-2,5,2',4',5'- and 4-MSF-2,5,2',3',4'-PenCB at respective doses of 5.2 and 5.8 ppm, which were about 35,000 times higher than the concentrations in the lungs and adipose tissue of healthy Japanese people, significantly enhanced the frequency of SCEs. 2) In the simultaneous treatment of one of the five MSF-PCB congeners and PenCDF (3.9 ppb), TCDD (1.5 ppb) or Co-PenCB (8.8 ppb), the combination of 3-MSF-4,5,3',4'-TCB (6.8 ppb) or 4-MSF-2,5,2',3',5',6'-HCB and one of the three highly toxic chemicals significantly promoted the formation of SCEs. We have already studied whether these MSF-PCBs are non-S-dependent genotoxic compounds or not and have obtained the results that they seemed not to be or very weak ones. Therefore, based on the results of this and our former studies, the five MSF-PCB congeners examined are considered rather potent S-dependent genotoxic chemicals than non-S-dependent ones.