Histological changes are shown of ossification induced by a simultaneous exposure to zinc and cadmium or to zinc and copper using embryonic chick femur in a culture system. Cadmium caused an atrophic change of the osseous tissue in the absence of zinc but caused an osteomalacic change with a partial degenerative change in the presence of zinc after a 6-day culture. Copper caused an atrophic change in the absence or presence of zinc. These observations were partly supported by the fact that the diaphysial calcium content was significantly decreased by zinc alone, and the decrease was unaffected by cadmium or copper. Zinc significantly decreased cadmium accumulation but not copper accumulation in the diaphysis. Thus, in spite of the inhibitory effect on calcification, zinc prevented a decrease in bone matrix formation caused by cadmium but not that by copper. Exposure of chick femur culture to zinc and cadmium induced changes consistent with osteomalacia, i.e., decreased mineralization of bone, with or without suppression of matrix formation. Exposure to zinc and copper, however, induced changes consistent with osteoporosis, i.e., decreased mineralization and matrix formation.