Estimating long-term effects of endocrine-disrupting chemicals on a species is important to assessing the overall risk to the populations. The present study reports the results of a 42-week exposure of estuarine sheepshead minnows (Cyprinodon variegatus) to the androgen, 17beta-trenbolone (Tb) conducted to determine if partial-(F0) or single-generation (F1) fish exposures identify multigenerational (F0-F3) effects of androgens on fish. Adult F0 fish were exposed to 0.007, 0.027, 0.13, 0.87,and 4.1 microg Tb/L, the F1 generation to < or =0.87 microg Tb/L, the F2 fish to < or =0.13 microg Tb/L, and the F3 fish to < or =0.027 microg Tb/L. The highest concentrations with reproducing populations at the end of the F0, F1, and F2 generations were 4.1, 0.87, and 0.027 microg Tb/L, respectively. Reproduction in the F0, F1, and F2 generations was significantly reduced at 0.87, 0.027, and 0.027 microg Tb/L, respectively. Fish were significantly masculinized in the F1 generation exposed to 0.13 microg Tb/L or greater. Female plasma vitellogenin was significantly reduced in F0 fish exposed to > or =0.87 microg Tb/L. Gonadosomatic indices of the F0 and F1 generations were significantly increased at 0.87 and 0.13 microg Tb/L in the F0 and F1 generation, respectively, and were accompanied by ovarian histological changes. Reproduction was the most consistently sensitive measure of androgen effects and, after a life-cycle exposure, the daily reproductive rate predicted concentrations affecting successive generations. The present study provides evidence that a multiple generation exposure of fish to some endocrine-disrupting chemicals can result in developmental and reproductive changes that have a much greater impact on the success of a species than was indicated from shorter term exposures.