In order to study the possible mutagenic properties of polychlorinated biphenyls (PCBs), human lymphocyte cultures were examined for chromosome breakage, rearrangements, sister-chromatid exchange, and mitotic delay. The present study, which used cyclophosphamide as a positive control, shows that one planar PCB congener, 3,4,3',4'-tetrachlorobiphenyl, caused dose-related chromosome breakage in human lymphocytes exposed in vitro to 0.1-10(-4) micrograms/ml. In contrast, the non-planar PCB, 2,5,2',5', did not cause chromosome damage in comparable tests even at concentrations as high as 1 microgram/ml. However, when 3,4,3',4' at a concentration lower than that which causes chromosome breakage (10(-5) micrograms/ml) was combined with a non-clastogenic concentration of 2,5,2',5', the chromosomal damage observed was far in excess of what one would expect from higher doses of 3,4,3',4' alone. These results suggest that some PCB congeners may interact to cause synergistic genotoxic effects.