The accumulation of Cd in rat liver Cd binding protein [CdBP] induced by single and repeated i.p. injections of CdCl2 and the de novo biosynthesis of CdBP were studied by using 109Cd to measure Cd binding in the CdBP and 35S incorporation as indicator of protein synthesis. The biosynthesis of CdBP is controlled by the Cd concentration. For single doses up to 1 mg Cd2+/kg body weight about 50% of the Cd is present in the soluble fraction of liver bound to CdBP and the incorporation of 35S-cysteine is linear with the Cd concentration. When single doses ranging from 1-3 mg Cd2+/kg body weight are administered the fractions of both 35S-cysteine and Cd incorporated into de novo synthesized CdBP gradually decrease. For single doses higher than 3 mg Cd2+/kg body weight the biosynthesis capability is maximum and 20 .mu.g Cd/g liver can be incorporated into the de novo biosynthesized CdBP. When rats are treated every day with amounts of Cd of about 0.8 mg Cd2+/kg body weight for up to 8 days a dose-proportional increase in both Cd incorporation and CdBP biosynthesis are observed. This shows a cumulative incorporation of Cd in the de novo biosynthesized CdBP. Experiments carried out by injecting 65ZnCl2 and 203HgCl2 every day showed that they are not accumulated like Cd and do not induce the biosynthesis of rat liver CdBP after repeated administration over 7 days.