An increasing number of studies have reported unexpectedly high body burdens of triphenyltin (TPT) in wild fishes around the world. To assess the effects of TPT on fish, we exposed pairs of medaka (Oryzias latipes) to different levels of TPT for 5 weeks, and the reproduction responses and transgenerational effects were studied. The results demonstrated that TPT exposure markedly suppressed the spawning frequency, spawned egg number, egg quality and gonad development, and induced teratogenesis, such as hemorrhaging, eye defects, morphological malformation and conjoined twins, less hatchability, and swim-up failure in the F1 generation, thereby resulting in a significant decrease in the capacity to produce viable offspring (p < 0.01). The residual TPT levels in the exposure fish are in the range of 6.52 +/- 0.56 to 5595 +/- 1016 ng of TPT/g of wet weight, similar to those reported in wild fish around the world, indicating TPT contamination in the real world would have a significant adverse effect on the health of fish population. Down-regulation of vitellogenin (VTG) genes in the female of the TPT exposure groups was recognized as a cause for the decreased fecundity. Expressions of VEGFs and PAX6 associated with vascular or ocular development respectively, were measured in hemorrhaging and eye defects embryos and showed good correlations with response outcomes.