Intravenous dopamine has been shown to increase renal plasma flow in man. The role of endogenous dopamine in the maintenance of renal plasma flow has not been described. We speculated that if endogenous dopamine activity is important in the maintenance of renal plasma flow, then high doses of a potent dopamine blocking drug such as metoclopramide would decrease renal flow. To test this hypothesis, we measured renal plasma flow using a single-injection technique with 131I-labeled orthoiodohippurate. Measurements were made before and after the administration of high doses of metoclopramide (1 to 2.5 mg/kg) to 20 patients receiving metoclopramide as an antiemetic before chemotherapy. Seven control subjects underwent sequential measurements of renal plasma flow without intervening metoclopramide dosing. Mean (+/- SD) renal plasma flow did not change in the control population (from 441 +/- 198 to 437 +/- 117 ml/min), but declined significantly in the patients who received metoclopramide (443 +/- 115 ml/min before metoclopramide and 387 +/- 137 ml/min after metoclopramide; P less than 0.001). In 25% of our study population the decline in renal plasma flow was greater than 20% below baseline levels. The magnitude of the effect did not appear to correlate with the pretreatment creatinine clearance, age, or sex of the patients. We conclude that high doses of metoclopramide decrease renal plasma flow in man. These data suggest a role for dopamine in the maintenance of renal plasma flow in patients receiving intravenous hydration. Changes of the magnitude we observed may well be of clinical importance. These findings therefore also suggest the possibility of metoclopramide potentiation of cisplatin nephrotoxicity.