Field experiments established that tetraploid soybean [Glycine max (L.) Merr.] plants were relatively tolerant while diploid plants were highly susceptible to metribuzin [4-amino-6-tert-butyl-3-(methylthio)-as-triazin-5(4H)-one] applied both preemergence and postemergence. Sensitivity of diploids and tolerance of tetraploids was also found in growth chamber experiments. Autoradiographs prepared 4 days after 14C-metribuzin application showed a high level of 14C-translocation to all parts of diploid plants including meristems. In contrast, only low levels of 14C were translocated in tetraploid plants, with no 14C-movement into meristems. Tetraploid plants rapidly transformed absorbed metribuzin to nontoxic products. Diploids were incapable of inactivating absorbed metribuzin at a rate sufficient to prevent injury. Differences in absorption, translocation, and metabolism of metribuzin appeared to be the main factors in the diploid and tetraploid differential response in field and growth chamber experiments. Differences in the rate of metribuzin metabolism appeared to be the factor responsible for the differential response in diploid and tetraploid cell suspension cultures. The primary polar metabolites were conjugates of metribuzin and deaminated metribuzin [6-tert-butyl-3-(methylthio)-1,2,4-triazin-5(4H)-one] with a ratio of 8:1, respectively.