Studies 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-1 of 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 with m- or p-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 of p-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-1 1,4-DCB. (TEA). The results of these studies demonstrated that ortho substitution enhanced hepatic and renal toxicity. The results also would suggest that the liver was more sensitive than the kidney for DCB toxicity.