Plasma and tumour concentrations of estramustine, estromustine, estradiol and estrone, the major metabolites of estramustine phosphate (estracyt), were determined in patients with prostatic carcinoma treated between one and nine years with repeated oral doses of estracyt (560 to 840 mg./day). The last dose was given 12 to 16 hours before sampling. The binding of radioactive estramustine and estromustine was determined in the tumour tissue to examine the possible role of estramustine-binding protein for the accumulation of these metabolites into the tumour. Comparison was made with benign prostate hyperplastic tissue from untreated patients. Estromustine was the main metabolite in plasma as well as in the tumour (range 235 to 450 and 205 to 485 ng./gm., respectively), whereas estramustine (20 to 45; 95 to 370), estrone (62 to 140; 63 to 160) and estradiol (8 to 15; 7 to 36) were found in lower concentrations. Interestingly the concentration of estramustine was as an average six times higher in the tumour than in plasma contrasting with the other metabolites which were present in equal amounts of the two localities. Binding of 3H-estramustine and 3H-estromustine was two to three times higher in the tumour than in benign hyperplastic tissue and negligible in plasma samples. The present study is the first where substantial amounts of cytotoxically active estramustine and estromustine are demonstrated in tumour tissue from estracyt treated patients. Our findings suggest a mechanism for selective uptake of these metabolites in prostatic cancer (estramustine-binding protein). The uptake and binding of estramustine and estromustine in the tumour may account for the clinical effects of estracyt in prostatic carcinoma.