The increased incidence of liver tumors in CFl mice fed dieldrin and certain other compounds (Thorpe and Walker, 1973) appears to constitute a species-specific effect. The general question of species specificity of action is fundamental to the selection of appropriate experimental species and such selection is particularly important in the field of carcinogenicity testing. A knowledge of the mechanism of action is a basic requirement for the accurate extrapolation of results obtained in experimental animals to man. Our investigations at Tunstall Laboratory have been orientated towards gaining an understanding of the mechanism of action of dieldrin on mouse liver and they have been wide-ranging in nature. The initial objectives of these studies were to define the loci of interaction in, and the effects of ingested dieldrin on, the livers of CFE rats, CFl mice, and dogs at the subcellular level (Wright et al., 1972). In view of the long-term effect of dieldrin on mouse liver we decided that it would be desirable to extend these studies to include a primate species. The rhesus monkey was selected for this purpose (Wright et al., 1972). At the start of these studies, it was known that dieldrin in large doses caused generalized liver enlargement in the rat, mouse, and dog. It was also clear that the longterm response of the CFl mouse differed from that in the rat. Thus the initial generalized enlargement of mouse liver was followed after about 1 year by an increased incidence of liver tumors. In all three species, the initial generalized liver enlargement was known to be associated with the enlargement of individual liver cells (hypertrophy). Studies in the rat had demonstrated that the enlargement was associated with the induction of the liver microsomal monooxygenase system and was reversible (Ghazal et al., 1964; Ferrigan et al., 1965). It seemed probable, therefore, that the dieldrin-induced enlargement of rat liver was a typical example of hyperfunctional liver enlargement which may be regarded as an overt manifestation of microsomal enzyme induction. Accordingly, a positive control compound was included in our studies. Phenobarbital was selected for two reasons. First, this compound was and remains the most studied microsomal enzyme inducer. Second, this drug had been used extensively in humans for protracted periods and at high dose levels. Phenobarbital was not included in the experiments with monkeys.