The chronopharmacokinetics of 4' epi-adriamycin (Epi) have been studied in ten patients with gynecological malignancies. The drug (45 mg m-2) was administered as a short time (5.0 min) intravenous infusion at 7 a.m. and 7 p.m., in a randomized cross-over design. The pharmacokinetics of Epi were evaluated according to the statistical moment theory. Morning and afternoon dosing of Epi was not bioequivalent. The area under the plasma concentration-time curve (AUC), the maximum plasma concentration (Cmax), mean residence time (MRT) and the terminal half-life time (t1/2) could differ by more than 35% after morning and afternoon dosing. The inter-individual variation of AUC and Cp,max were larger after morning dosing than after afternoon dosing (P less than 0.04). The morning dose of Epi resulted in higher values of AUC in seven of the ten treated patients as compared to the afternoon dose. The terminal half-life times were shorter in eight of the patients after the morning dose.