Uptake of Cd2+ by the liver and kidney of female mice 24 hr after challenge with a large dose of Cd2+ (100 mg Cd2+/kg, p.o.) was greatly reduced by pretreatment with a small dose of the cation (15 mg Cd2+/kg, p.o.) at 24 hr (for liver) and at 6, 24 or 48 hr (for kidney) prior to the challenge dose. The hepatic concentration of Zn2+ tended to be increased by the Cd2+ challenge and was increased further by pretreatment. The renal concentration of Zn2+ was not influenced by Cd2+ administration. The retention rate of Cd2+ in the stomach and its contents 24 hr after the Cd2+ challenge was decreased by pretreatment. In addition, the excretion rate of Cd2+ into the feces 24 hr after the Cd2+ challenge was increased by pretreatment at 6 to 24 hr prior to the challenge dose. Consequently, the absorption rate of Cd2+ 24 hr after the Cd2+ challenge was markedly reduced by pretreatment at 24 hr prior to the challenge dose. The urinary and biliary excretion of Cd2+ was very low. The motility of the small intestine was stimulated 6 hr after a small dose of Cd2+, but returned to normal within 24 hr. The motility tended to be reduced 4 hr after the Cd2+ challenge, but conversely, it was facilitated at 24 hr. Pretreatment at 6 or 24 hr prior to the challenge dose prevented the reduction of the motility 4 hr after the Cd2+ challenge.