2-Methoxyoestradiol (2-MeOE2) is an endogenous oestrogen metabolite that inhibits the proliferation of cancer cells in vitro, and it is also antiangiogenic. In vivo 2-MeOE2, when administered at relatively high doses, inhibits the growth of tumours derived from breast cancer cells, sarcomas and melanomas. Sulphamoylated derivatives of 2-MeOE2 are more potent inhibitors of in vitro breast cancer cell growth than 2-MeOE2. In the present study, we have compared the pharmacokinetic profiles and metabolism of 2-MeOE2 and its sulphamoylated derivative, 2-methoxyoestradiol-bis-sulphamate (2-MeOE2bisMATE), in adult female rats. Their ability to inhibit tumour growth was compared in nude mice bearing xenografts derived from MDA-MB-435 (oestrogen receptor negative) melanoma cancer cells. After a single oral 10 mg kg(-1) dose of 2-MeOE2bisMATE, significant concentrations of this compound were still detectable at 24 h. In contrast, no 2-MeOE2 or metabolites were detected in plasma at any time after a 10 mg kg(-1) oral dose. Thus, the bioavailability of 2-MeOE2 is very low, whereas for 2-MeOE2bisMATE it was 85%. No significant metabolites of 2-MeOE2bisMATE were detected in plasma after oral or intravenous dosing, showing that this drug is resistant to metabolism. In the tumour efficacy model, oral administration of 2-MeOE2bisMATE, at 20 mg kg(-1) day(-1) daily for 28 days, almost completely inhibited tumour growth. Inhibition of tumour growth was maintained for a further 28 days after the cessation of dosing. At this dose level, 2-MeOE2 did not inhibit tumour growth. The resistance to metabolism shown by 2-MeOE2bisMATE and its ability to inhibit tumour growth in vivo suggest that this compound should have considerable potential for development as a novel anticancer drug.