The hypothesis that the prior intake of barbiturates may predispose patients to form increased amounts of oxalate following the intravenous infusion of xylitol was investigated in the rat. Phenobarbitone pre-treatment resulted in a 2-3 fold increase in urinary [14C] oxalate concentration following the intraperitoneal injection of [U-14C] xylitol or [l -14C] glycollate. The absence of any marked changes in urine volumes and creatinine excretion implied that this increase in urinary oxalate excretion was due to the enhanced synthesis of oxalate. The activities of key enzymes in hepatic oxalate synthesis, glycollate oxidase, lactate dehydrogenase, catalase and alanine aminotransferase were not altered by phenobarbitone pre-treatment. It is suggested that the increased activity of the microsomal mixed function oxidases, following phenobarbitone treatment, may facilitate the oxidation of glycollate and possibly xylitol. This communication leads experimental support to the concept that the prior intake of drugs, such as barbiturates, may predispose patients to form increased amounts of oxalate.