1. Tamoxifen is used for the prevention and treatment of oestrogen receptor-positive breast cancer. 2. Tamoxifen is metabolized extensively and the formation of Z-4-hydroxy-tamoxifen (Z-4-OH-tam), a potent anti-oestrogen with high affinity for the oestrogen receptor, is believed to be strongly related to the therapeutic benefit achieved following tamoxifen treatment. 3. In vitro studies using human liver microsome preparations have shown considerable interindividual variability in the formation rates of Z-4-OH-tam. 4. Cytochrome P450 (CYP) isoform-specific chemical and monoclonal antibody inhibition studies have demonstrated that CYP2B6, CYP2C9, CYP2D6 and CYP3A4 all mediate the formation of Z-4-OH-tam. 5. Significant associations between the percentage inhibition of Z-4-OH-tam by CYP isoform-specific inhibitors and the rate of metabolism of CYP isoform-specific index reactions and between individual expression of CYP2B6, CYP2C9 and CYP2D6 and Z-4-OH-tam formation rates indicate predominant roles for these isoforms in this pathway. 6. Genotyping of patients with regards to CYP2B6, CYP2C9 and CYP2D6 may play a role in prediction of Z-4-OH-tam formation and, consequently, ultimate therapeutic benefit of tamoxifen treatment.