Treatment of mature female tilapia (Oreochromis niloticus) with high levels of androgen (17 alpha-methyltestosterone, 17 alpha MT) results in a pronounced decline in plasma vitellogenin levels as determined by gel electrophoresis. Total RNA extracted from livers of treated fish and vehicle-injected controls was analyzed by Northern and slot blot hybridization using an oligonucleotide complementary to a sequence in the 3' end of tilapia vitellogenin mRNA. The probe revealed an mRNA of 6.5 kb in liver from the control mature female fish which was decreased by 85% by androgen treatment. As expected, estradiol (E2) treatment induced the 6.5-kb mRNA in mature male tilapia. The antiestrogen, tamoxifen, strongly decreased vitellogenin mRNA levels in mature females. Radioimmunoassay of serum from control and 17 alpha MT-treated female tilapia showed a marked reduction in serum E2 levels, from 11.4 +/- 2.6 ng/ml in controls to 2.2 +/- 0.13 ng/ml in treated fish. Tamoxifen, however, resulted in increased serum E2 levels, probably by blocking E2 negative feedback. The serum E2-lowering effect of 17 alpha MT suggests an inhibitory site of action on gonadotropin production at the hypothalamic-pituitary axis, possibly through an androgen receptor or through an estrogen receptor after local aromatization of 17 alpha MT.