The present study was undertaken to evaluate the potential cancer chemopreventive effects of novel synthetic derivatives of isoflavones. Initially these agents were tested in a mouse mammary organ culture (MMOC) model. Phenoxodiol (2H-1-benzopyran-7-O1,3-(4-hydroxyphenyl)), the most effective in this assay, was selected for further testing in female Sprague-Dawley rats. The agent was tested at 0 (basal diet), 50 and 75 mg/kg diet. Mammary carcinomas in these three groups were induced by dimethylbenz[a]anthracene (DMBA) injected 1 week after the animals started eating the experimental diets. Phenoxodiol significantly reduced tumour incidence rate at both doses (P<or=0.05). Tumour latency was increased from 70.4 days in the control group to 92.9 (P=0.04) days and 97.8 (P=0.03) days in the groups that were fed 50 and 75 mg/kg phenoxodiol, respectively. Compared with the control that was fed basal diet, tumour multiplicity was reduced by 42% (P=0.04) in the group that was fed 50 mg/kg phenoxodiol and by 49% (P=0.01) in the group that was fed 75 mg/kg phenoxodiol. Two additional groups that were not exposed to DMBA, one fed the basal diet and the other a diet containing 75 mg/kg phenoxodiol, were free of tumours. These data suggest that phenoxodiol is an effective chemopreventive agent against DMBA-induced mammary carcinogenesis.