Hexachloro-1,3-butadiene (HCBD) produced a time- and dose-related increase in hepatic water content following i.p. administration to male Alderley Park (Alpk/AP) mice. The increase in liver water was maximal 1-2 days after a single dose of 50 mg kg-1 and had returned to normal by day 5. Associated with the increased water, there was a parallel increase in Na+ and K+ ions, with no overall change in intracellular cation concentration. Liver non-protein sulphydryl content showed no consistent time-related decrease after 50 mg kg-1 HCBD. Histopathological examination of the liver showed fine cytoplasmic vacuolation of periportal hepatocytes which was more marked following 100 or 200 mg kg-1 than 50 mg kg-1 HCBD. In one animal, following 200 mg kg-1 HCBD, the liver showed ballooning and degeneration of periportal hepatocytes. Ultrastructural changes were evident 4 h after 50 mg kg-1 and consisted of mitochondrial swelling in periportal hepatocytes, whilst pericentral hepatocytes appeared normal. By 16 h, marked mitochondrial swelling and some proliferation of smooth endoplasmic reticulum were evident in periportal hepatocytes. Male mice of the C57BL/10J and C3H strains appeared to be more sensitive to HCBD-induced hepatic hydropic change than did the male and female Alpk/AP strain and male Balbc and DBA/2J strains. It appears that HCBD or a metabolite causes disruption of mitochondria in periportal hepatocytes which results in an influx of water and ions into the cell without compromising the Na+ pump.