d-Serine is nephrotoxic in rats. Based on circumstantial evidence, it has been suspected that d-amino-acid oxidase is involved in this nephrotoxicity. Since we found that LEA/SENDAI rats lacked d-amino-acid oxidase, we examined whether this enzyme was associated with d-serine-induced nephrotoxicity using the LEA/SENDAI rats and control F344 rats. When d-propargylglycine, which is known to have a nephrotoxic effect through its metabolism by d-amino-acid oxidase, was injected intraperitoneally into the F344 rats, it caused glucosuria and polyuria. However, injection of d-propargylglycine into LEA/SENDAI rats did not cause any glucosuria or polyuria, indicating that d-amino-acid oxidase is definitely not functional in these rats. d-Serine was then injected into the F344 and LEA/SENDAI rats. It caused glucosuria and polyuria in the F344 rats but not in the LEA/SENDAI rats. These results indicate clearly that d-amino-acid oxidase is responsible for the d-serine-induced nephrotoxicity.