Summary.-Using the DMBA-induced mammary tumour as a model, the effect of hormone manipulation on steroid sulphurylation and on oxidative and reductive metabolism has been investigated. or oestradiol-17p + progesterone, administered to oophorectomized animals, had no effect on adenosine-3'-phosphate-5'-phosphosulphate formation in the tumours. Dehydroepiandrosterone sulphotransferase was also unaffected. A large increase in oestrogen sulphotransferase following administration of oestrogen + progesterone was observed in some but not all tumours, and the overall results were not statistically significant. The major metabolities of dehydroepiandrosterone, by both human and carcinogen-induced rat mammary tumours in vitro, are 7-oxygenated derivatives. Oestrogen administration led to a significantly decreased production of total 7-oxygenated derivatives of dehydroepiandrosterone. Conversion to 5-androstene-3p,17p-diol was unaffected by the hormones. The rate of formation of oestradiol-17p from oestrone was increased 5-fold in growing tumours from animals receiving oestrogen, or oestrogen+proges-terone, compared to regressing tumours in oophorectomized control animals.A HYPOTHESIS has been presented implicating adrenal dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) in the aetiology of human breast cancer (Adams, 1977). The main metabolites of DHEA, produced by in vitro incubation with human mammary tumours, are 7-oxygenated derivatives (7a-hydroxy DH-EA, 7P-hydroxy DHEA and 7-oxo DHEA) and 5-androstene-3g, 17/-diol (Li et al., 1978). The latter can cause translocation of the oestrogen receptor in both the uterus and mammary tumours Nicholson et al., 1978). Although it is difficult to be certain of the exact role played by the 7-hydroxylation system in mammary tissue, it has been suggested ) that it could function as an inactivation step to modify oestrogen receptor translocation by 33-hydroxy-A5-androstenes, which are known to occur in relatively high concentrations in human mammary tumours (Maynard et al., 1977). Thus high levels of DHEAS in the blood could lead to high intracellular levels of DHEA and its metabolites formed in situ in mammary tissue.Pathways of DHEA metabolism similar to those established in human mammary tumours also occur in 7,12-dimethylbenz-(a)anthracene (DMBA)-induced rat mammary tumours (Li et al., 1976). It was thus of interest to use this as a model to study the influence of an altered sexhormone milieu in tumour-bearing rats upon subsequent DHEA metabolism in the tumour. In parallel studies, the influence of an altered hormone milieu on oestrogen metabolism by these tumours has been investigated.One other aspect of DHEA metabolism by human mammary tumours, i.e. formation of the sulphate ester, is of relevance when considered together with the sulphurylation of oestradiol-17/. Measurement of these conversions by the tumour