AbstractStudies were conducted to examine acute hepatic and renal toxicity of dichlorobenzene (DCB) structural isomers. Male Fischer 344 (F344) rats were injected with 2, 3 or 4 mmol kg−1of 1,2‐DCB, 1,3‐DCB or 1,4‐DCB (o−, m−, p−). Pair‐fed control (PFC) animals were injected (i.p.) with corn oil (1 ml kg−1). Hepatic and renal toxicity was quantitated 24 h after injection of DCB or vehicle. Plasma transaminase (ALT/GPT) activity was increased (P<0.05) by 1,2‐DCB as a function of dose administered. Centrilobular necrosis was observed in rats treated with 1,2‐DCB while morphology was relatively normal in rats treated withm‐ orp‐DCB. Administration of (2 or 4 mmol kg−1) 1,3‐DCB or 1,4‐DCB did not alter kidney weight or blood urea nitrogen (BUN) levels. Renal cortical slice accumulation ofp‐aminohippurate (PAH) was decreased (P<0.05) by (2 and 4 mmol kg−1) 1,3‐DCB and (3 and 4 mmol kg−1) 1,2‐DCB while accumulation of the cation tetraethylammonium (TEA) was decreased by 4 mmol kg−11,4‐DCB. (TEA). The results of these studies demonstrated thatorthosubstitution enhanced hepatic and renal toxicity. The results also would suggest that the liver was mo