Studies have been carried out upon the in vitro metabolism of the dieldrin analogs 14C-labeled 1,2,3,4,9,9-hexachloro- exo-5,6-epoxy, 1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene (HCE) and 14C-labeled 1,2,3,4,9,9-hexachloro-6,7-epoxy 1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene (HEOM) by liver microsomes of the rat, rabbit, pigeon, and Japanese quail. HCE was degraded mainly by microsomal monooxygenase attack, to give a major primary metabolite and two secondary metabolites. Epoxide hydratase degraded HCE relatively slowly to give a trans-diol. HEOM was also attacked by both enzymes although there was reasonable balance here between the two types of enzymatic attack. In vivo studies were conducted upon the same four species following intraperitoneal injection of 14C-labeled HCE, HEOM, and dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy 1,4,4a,5,6,7,8,8a-octahydro- exo-1,4- endo-5,8-dimethanonaphthalene) (HEOD). The output of metabolites was measured in urine and feces. Biliary excretion was measured using animals fitted with reentrant cannulae. Pigeons were colostomized to allow the separate collection of urine and feces. For HCE, there was a similar pattern of metabolism both in vivo and in vitro. The same sequence of primary and secondary oxidation was found in both situations. There were differences between the in vivo and in vitro metabolism with regard to certain minor metabolites and the relative amounts of trans-diol formed. In further work with the male rat the rates of metabolism of the different compounds in vivo and in vitro were compared. Both HCE and HEOM were metabolized relatively rapidly in vitro, and the rate at which the metabolites of HCE were excreted in the bile was not increased after induction with phenobarbital, even though induction caused a 17-fold increase in microsomal enzyme activity per gram of liver. On the other hand the biliary excretion rate of metabolites of dieldrin increased about threefold following induction. It appears that the rate of excretion of HCE or HEOM is dependent upon the rate at which each is available to the liver, this being very much lower than the maximal velocity of enzymatic degradation in both cases. On the other hand the metabolic rate is very slow in the case of dieldrin and apparently limits the rate at which its metabolites are excreted. It may be possible to define a threshold in vitro metabolic rate for these highly liposoluble insecticides, below which the excretion rate is limited by the rate of enzymatic attack.