The metabolism of three tetrachlorobenzene isomers (TeCB) was investigated in the squirrel monkey. The animals were administered orally 6 single doses of14C‐labeled 1,2,3,4‐, 1,2,4,5‐, or 1,2,3,5‐tetrachlorobenzene over a 3‐wk period at levels ranging from 50 to 100 mg/kg body weight (b.w.) and kept in individual metabolism cages to collect urine and feces for radioassay. Approximately 38% (1,2,3,4‐TeCB), 36% (1,2,3,5‐TeCB), and 18% (1,2,4,5‐TeCB) of the doses were excreted respectively in the feces 48 h postadministration. In monkeys dosed with 1,2,3,4‐TeCB, unchanged compound accounted for 50% of the fecal radioactivity; its fecal metabolites were identified as 1,2,4,5‐tetrachlorophenol (TeCP, 22%), U‐acetyl‐S‐(2,3,4,5‐tetrachloro‐phenyl) cysteine (18%), 2,3,4,5‐tetrachlorophenyl sulfinic acid (3%), 2,3,4‐trichloro‐phenyl methyl sulfide (0.6%), and 2,3,4,5‐tetrachlorophenyl methyl sulfide (0.2%). As was the case with 1,2,3,4‐TeCB, unchanged compound accounted for more than 50% of the fecal radioactivity found in the monkeys dosed with 1,2,3,5‐TeCB. The fecal metabolites of 1,2,3,5‐TeCB consisted of 2,3,4,5‐TeCP (2%), 2,3,4,6‐TeCP (14%), 2,3,5,6‐TeCP (9%), and 2,3,5,6‐tetrachlorophenyl sulfinic acid (15%). No metabolites were detected in the feces of monkeys dosed with 1,2,4,5‐TeCB. While the fecal route represented the major route of excretion for 1,2,3,4‐TeCB, the other two isomers were eliminated exclusively in the feces. The above data in the squirrel monkey are different from those obtained with the rat and the rabbit, and demonstrate the different metabolic pathways for the isomers.