The pharmacokinetics and tissue distribution of Ml-M4 were compared after intravenous administration of DA-125,25 mg kg-I, to BDF, mice (n = 5 at each sampling time) and subcutaneously implanted Lewis-lungcarcinoma-bearing BDF, mice (n = 10 at each sampling time). The mean plasma concentrations of Ml-M4 were not significantly different between the two groups of mice, and hence similar pharmacokinetic parameters for Ml-M4 were obtained. The amount of M1 in the lung was sigtllficantly greater in the tumour-bearing mice than in the control mice, resulting in a greater AUA, in the tumour-bearing mice (1 8 600 against 8940 pg min g-I), and vice versa in the liver (962 against 3840 pg min g-l). However, the corresponding values for other tissues were comparable between the control and tumourbearing mice. The amount of M1 was greatest in the lung for up to 2 h in the tumour-bearing mice. M2 was the predominant metabolite among Ml-M4 excreted in 24h urine by both groups of mice; 8.36 and 10.7% of the IV dose were excreted in 24 h urine as M2 -expressed in terms of DA-125-by the control and tumour-bearing mice, respectively. The amount of M1 in the tumour mass reached a mean C,, of 3.75pgg-I immediately after IV administration of DA-125 to the tumour-bearing mice, then declined very slowly to an amount that remained almost constant for up to 24 h. This suggested that M 1 has high affinity for the subcutaneously implanted Lewis lung carcinoma. The antitumour activity, such as the increase in life span (ILS) and tumour growth inhibition (TGI) of DA-125,6-48 mg kg-I, and adriamycin (ADM), 3-18 mg kg-I, were also compared in subcutaneously implanted Lewislungcarcinoma-bearing BDF, mice after four weekly IV administrations of the drugs on days 1,8,15, and 22 following tumour implantation. More than three out of six mice survived as tumour-free for longer than 70 d at a DA-125 dose range of 6-24mg kg-I, but there were no tumour-free mice at any dose of ADM. Assuming ILS values higher than 30% to be effective, DA-125 doses ranging from 6 to 24mg kg-' were effective in increasing the life span, which ADM does only within the dose range of 612mg kg-I.