Administration of hexachloro-1:3-butadiene (HCBD) intraperitoneally at a dose of 50 mg/kg body weight caused necrosis of the proximal tubule of the mouse kidney. The earliest morphological changes detectable by light microscopy were observed after 4 h, and by 16 extensive proximal tubular necrosis was seen throughout the cortex. Active tubular regeneration was apparent by day 5 and by day 14 substantial recovery of morphology had occurred. In the electron microscope mitochondrial swelling was seen 1 and 2 h after dosing in the S1 and S2 segments of the proximal tubule, whereas by 4 and 8 h the major pathological changes were confined to the lower S2 and S3 segments and consisted of mitochondrial swelling and cellular necrosis. The extent of renal injury and regeneration correlated well with measurement of renal function. In conclusion, HCBD produces necrosis of the S2 and S3 segments of the proximal tubule in the mouse, this pattern of injury is different from that seen in the rat where HCBD produces selective necrosis of the S3 segment.