Weekly low-dose injections of 20 mg 4'-epi-adriamycin (E-ADM) were given to 12 patients with advanced postmenopausal breast cancer for at least 8 weeks. In advance, all patients were given hormonal therapy and polychemotherapy not containing anthracyclines. E-ADM concentrations in plasma and urine and in blood and bone marrow cells were determined during 8 consecutive weeks. Plasma concentrations in the range of a few nanograms per milliliter were seen up to 72-96 h. Cellular concentrations appeared to be more than 100-fold the plasma concentrations, and were 190 +/- 66 ng/10(9) cells on day 8, before the next injection was given. Nevertheless, no serious bone marrow toxicity was observed. In two patients with an increased plasma bilirubin concentration, cellular E-ADM concentrations were 20%-40% higher than those observed in the other patients. Plasma concentrations of E-ADM and 4'-epi-adriamycinol showed terminal half-lives 2-3 times longer and could be followed throughout the week. In three patients biopsies of skin metastases were examined. In two patients E-ADM could be demonstrated in the tumor tissue up to 7 days after the last injection. Although the number of patients investigated is too small to relate the drug kinetics to clinical response, it is of interest that the two patients with the highest cellular E-ADM concentrations responded better than the others.