It is well known that zinc is an essential micronutrient and, as a rule, organisms keep relatively constant low levels of zinc to maintain cellular functions. The squirrelfish family (Holocentridae) is the only known exception from this rule. Squirrelfish accumulate very high concentrations of zinc in the liver. In the present study, we demonstrate that, while female squirrelfish store large amounts of zinc in the liver and ovaries, the males show zinc levels that are typical for vertebrates. The zinc content of the diet is the same in males and females, and zinc is not lost from the liver during starvation. Thus, the difference between genders in zinc storage is not dependent upon the diet. Rather, there are at least two processes that contribute to the accumulation in females. First, females possess high levels of two major zinc-binding proteins: metallothionein (MT) and a novel female-specific zinc-binding protein (FZnBP). In females, but not in males, almost all MT is present in the hepatocyte nucleus. FZnBP is exclusively found in the hepatocyte cytosol of females. Second, hepatocytes of female squirrelfish have a high capacity to transport zinc across the plasma membrane. In addition to the liver, only the gonads of females showed unusually high concentrations of zinc. Administration of exogenous oestrogen to females decreases the hepatic zinc concentration while there is a matching increase in the zinc content of the ovaries. Thus, oestrogen may trigger a redistribution of zinc from liver to ovaries. Together, our findings suggest that female squirrelfish may be uniquely adapted to detoxify zinc and to utilize it as a macronutrient for processes related to reproduction.