Experiments were performed to determine whether water-soluble contrast media (CM) show nephrotoxic properties when injected into rats after multiple renal insults. The latter consisted of combinations of prostaglandin synthesis inhibition (with indomethacin) and/or salt depletion and/or uninephrectomy. Renal function was evaluated by standard clinical methods to measure parameters such as urinary output, urinary osmolality, urinary creatinine excretion and serum creatinine. CM injected after prostaglandin synthesis inhibition alone did not influence urinary creatinine excretion or serum creatinine. After a combination of renal insults a significant increase in median serum creatinine values from 61.88 mumol/l [interquartile range (IR) 17.68] [0.70 mg% (IR 0.20)] to 97.24 mumol/l (IR 79.56) [1.10 mg% (IR 0.90)] was observed but CM or sham injections did not prevent a normalization of serum creatinine. The pattern of recovery of serum creatinine was not influenced by previous kidney mass reduction. It is concluded that the nephrotoxic properties of CM cannot be detected with standard clinical methods in rats after multiple renal insults.