Previous study from our laboratory has demonstrated that infusion of uremic plasma ultrafiltrate to normal rats suppressed their calcitriol synthesis. In order identify the uremic toxins responsible for the suppression of the calcitriol synthesis, we studied the effects of known uremic toxins: spermidine, spermine, methylguanidine (MG), and guanidinosuccinic acid (GSA) on calcitriol metabolism in the rats. Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were measured in normal rats after they were infused for 24 hours with approximately 10 ml of normal saline containing one of the following substances: 0.8 mumoles spermidine, 0.3 mumoles spermine, 150 micrograms MG and 180 micrograms GSA. Control groups of rats were infused with 10 ml of normal saline for 24 hours. MCR of calcitriol was not altered by the infusion of each toxin; however, plasma concentration of calcitriol (controls, 105.3 +/- 6.7 pg/ml; versus GSA, 58.9 +/- 2.5 pg/ml, p less than 0.001) and PR of calcitriol (controls, 39.0 +/- 2.9 ng/kg/day, versus GSA, 22.5 +/- 1.62 ng/kg/day, p less than 0.001) were significantly suppressed by the infusion of GSA. The concentration (1.8 mg/dl) of GSA in the infusate was similar to that in the uremic plasma ultrafiltrate (2.32 +/- 1.41 mg/dl) used in the previous study, though the total amount of GSA infused to the rats was lower in the present study. GSA is, therefore, considered a uremic toxin that suppresses calcitriol synthesis.