In a study of the hepatic effects of Mirex (dodecachloroctahydro-1,3,4-methano-2H-cyclobuta[cd]pentalene), male Charles River CD-1 mice were fed 1–90 ppm Mirex in the diet for periods ranging from 1 to 70 wk. At regular intervals, heavy mitochondrial, light mitochondrial, microsomal, and soluble fractions were prepared from livers of three to six animals per group. Measurements of relative liver weight, DNA, protein, respiration, respiratory control, mitochondrial membrane permeability, mixed function oxidases ( N-demethylation, aromatic hydroxylation, and cytochrome P-450), glucose-6-phosphatase, diene conjugates, and protein binding were carried out. Mirex caused an increase in relative liver weight, total liver DNA, total protein in each liver fraction, mitochondrial respiration and coupling, and mixed function oxidases. Except for DNA, each parameter increased with an increase in the level of Mirex in the diet and the duration of feeding. DNA was stimulated at all doses to 130–150% of control levels. A further rise in DNA occurred during the onset of the development of liver nodules. The action of Mirex on mitochondria occurred predominantly in the light mitochondrial fraction and resulted in a stimulation of respiration, increased coupling and a decrease in membrane permeability. Mirex added to control mitochondria ( in vitro) produced none of these changes. Glucose-6-phosphatase activity was decreased with increasing levels of Mirex in the diet and duration of feeding. The concentration of microsomal diene conjugates was not affected by Mirex. Mirex was formly bound to soluble liver proteins both in vivo and in vitro, but did not displace cortisol from the cortisol receptor protein.