To investigate the interaction between Cd and Cu in relation to the content of collagen in bone, femurs obtained from 9-day-old chick embryos were cultivated with a combination of Cd and Cu concentrations of 8.9 μm and below for 4 days. When 2.23 or 4.45 μm Cd was added to the medium containing 4.45 or 8.90 μm Cu, the presence of both Cd and Cu caused a remarkable decrease in collagen synthesis compared with a decrease in collagen synthesis caused by either Cd or Cu alone. The results show that Cd and Cu caused an interactive inhibition of collagen synthesis, which was not due to an increase in collagen degradation by Cd and Cu. At concentrations showing inhibition, Cd caused an increase in Cu content and Cu caused an increase in Cd content. The increase in Cd content was mainly caused by the accumulation of Cd in bone mineral. The increase in Cu content was due to binding to metallothionein-like protein in the cytosol induced by Cd. The relationship between inhibition and the increase in both Cd and Cu was not confirmed after division of the bone into diaphysis and epiphysis. The present study showed that Cu aggravated the bone matrix damage caused by Cd.