We determined the amount of tamoxifen, N-desmethyltamoxifen (metabolite X), N-desdimethyltamoxifen (metabolite Z), and hydroxylated metabolites (Y, B, BX) in brain metastases from breast cancer and in the surrounding brain tissues. Specimens were collected from the breast cancer patients who received tamoxifen for 7-180 days and with the last dose taken within 28 h before surgical removal of the tumour. The concentrations of tamoxifen and its metabolites were up to 46-fold higher in the brain metastatic tumour and brain tissue than in serum. Metabolite X was the most abundant species followed by tamoxifen and metabolite Z. Small but significant amounts of the hydroxylated metabolites, trans-1(4-beta-hydroxyethoxyphenyl)-1,2-diphenylbut-1-ene (metabolite Y), 4-hydroxytamoxifen (metabolite B) and 4-hydroxy-N-desmethyltamoxifen (metabolite BX) were detected in most specimens. The ratios between the concentrations of tamoxifen and various metabolites were similar in tumour, brain and serum. This is the first report on the distribution of tamoxifen and metabolites into human brain and brain tumour, and the data form a basis for further investigation into the therapeutic effects of tamoxifen on brain metastases from breast cancer.