Blood 5-HIAA-14C levels derived from exogenous D,L-5-HTP-14C were investigated in normal, sham-operated and nephrectomized rats pretreated with MK-486 and probenecid (200 mg/kg i.p.). Blood 5-HIAA-14C levels decreased in nephrectomized rats following probenecid. Peripheral decarboxylase inhibition by MK-486 was enhanced by both probenecid and nephrectomy. Increased penetration of 5-HTP into brain occurred following probenecid. The results indicate that following MK-486 about 20% of the blood 5-HIAA-14C derived from 5-HTP-14C in rats originates in the CNS.