The protease inhibitor antipain is known to modulate the number of chromosomal aberrations induced by the S-phase-dependent alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Experiments have now been carried out to see if antipain might also effect the yield of aberrations induced by X-rays, which are S-independent and thus produce chromosomal aberrations by a different mechanism. The results show that human lymphocytes exposed to 0.4 or 1.5 Gy of X-rays at 48 h of culture and fixed at 3, 6, 8, 10 or 12 h thereafter contain 27-52% fewer chromatid breaks if the cells are also treated with antipain before irradiation. Because previous studies postulated that antipain could affect the induction of chromosomal aberrations by suppressing free radical reactions within cells, we also tested whether antipain affects X-ray-induced aberrations when present only during the time of irradiation, as is the case for free radical scavengers, such as L-cysteine. The results indicate that, in contrast to L-cysteine, antipain can suppress the induction of X-ray-induced aberrations even when administered as late as 2 h after irradiation, suggesting that the effects of antipain on aberrations are not attributable to its interference with short-lived radicals within the cells. Although the exact mechanism whereby antipain decreases the yield of chromosome aberrations induced by the S-independent agent X-rays is unknown, these data indicate that the formation of chromosome aberrations by S-independent agents too can involve an antipain-sensitive process.