This study is to compare the pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone (Mit-lipo) and free mitoxantrone (Mit-free). The antineoplastic effect of Mit-lipo was evaluated on PC-3 human xenograft tumor model after repeated intravenous injection at dose levels of 1, 2 and 4 mg x kg(-1). The pharmacokinetic study of Mit-lipo and Mit-free was performed on dogs following a single intravenous injection. The tissue distribution of Mit-lipo and Mit-free was observed on S-180 bearing mice after a single intravenous injection. (1) Pharmacodynamics: Mit-lipo dose-dependently inhibited PC-3 tumor growth at a dose ranging from 1 to 4 mg x kg(-1). The antitumor effect studies showed that Mit-lipo significantly improved the therapeutic effect in comparison with free drug. (2) Pharmacokinetics: in comparison with Mit-free, the AUC and t(1/2) values of Mit-lipo at the same dose level were higher than those of Mit-free in Beagle dogs. The results showed that Mit-lipo had long circulation characteristics. (3) Tissue distribution in S-180 bearing mice: compared to Mit-free, Mit-lipo preferentially accumulated into tumor zones instead of normal tissues. Tumor AUC in Mit-lipo treated animals was 8.7 fold higher than that in mice treated with the same dose of Mit-free. The Cmax values of Mit-lipo in heart, kidney, lung, spleen and intestinal tissue in Mit-lipo were 30.2%, 161.6%, 20.2%, 27.9% and 78.3% lower than those of Mit-free, respectively. The pharmacokinetics and tissue distribution of Mit-lipo changed obviously, thus increasing therapeutic effect and improving drug therapeutic index.