Pretreatment with nickel has earlier been shown to protect against cadmium intoxication. The effect of cadmium pretreatment on the nephro- and hepatotoxicity of nickel has been investigated. The administration of cadmium (6 mg/kg, i.m., once) to rats significantly enhanced urinary excretion of ALP, LDH, GOT, amino acids and proteins and increased the activity of serum ALP, GOT, and GPT, while the administration of nickel (6 mg/kg, i.p., 3 days) altered these parameters less significantly. These changes in urine and serum were used as a measure of renal and hepatic damage. The administration of nickel for three days, one week after cadmium treatment, caused significantly more marked enzymuria, aminoaciduria, proteinuria and an increase in the activity of serum enzymes than induced by either of them individually. However, cadmium pretreatment had no influence on urinary excretion or hepatic uptake of nickel, but increased renal uptake of nickel on the fourth day. The results suggest that cadmium enhances the nephro- and hepatotoxicity of nickel.