To clarify a possible mechanism of zinc (Zn)-induced tolerance to cadmium (Cd) toxicity on bone formation, femurs from 9-day-old chick embryos were cultured for 6 days by the roller-tube method in the presence of Cd (2, 4 or 9 microM) and/or Zn (60 microM). Zn prevented a decrease in bone growth caused by Cd at 4 and 9 microM. An increase in calcium (Ca) content of diaphysis was inhibited by Zn in both the presence and absence of Cd. Histologically, Zn protected a Cd-induced degenerative change of mesenchymal cells in the periosteum and that of osteoblasts around the trabecula at each Cd level. At 60 microM Zn, Cd accumulated less in the bone at 2 microM but more at 9 microM. From these results, it was concluded that Zn prevented Cd-induced toxicity in the process of ossification except calcification in a culture system by two different mechanisms, i.e. a decreasing Cd accumulation at a low level of Cd and probably an induction of metallothionein (MT)-like protein at a high level of Cd.