Since dietary protein increases urinary dopamine (DA) excretion in animals, this study was undertaken to assess the role of DA production in the acute changes in renal function following protein ingestion in man. Excretion of DA, sodium, potassium, water, solute, and creatinine were measured in six normal men in 30-min intervals over 5 h after oral ingestion of protein and/or carbidopa, an inhibitor of DA formation from 3,4-dihydroxyphenylalanine (DOPA). Overall, protein increased urinary DA 50% (P = 0.031) while carbidopa reduced it 70% (P less than 0.0001), although suppression of DA excretion by carbidopa was not uniform over the 5 h of observation. Carbidopa doubled the level of DOPA in venous plasma and greatly magnified the DOPA response to protein. Inhibition of decarboxylase activity reduced excretion of sodium, potassium, solute and water after protein ingestion. These results indicate that extraneuronal DOPA decarboxylation in kidney contributes to acute protein-induced changes in renal function in man and suggest a general role for the decarboxylation of circulating DOPA in the expression of dopaminergic effects on the kidney in vivo.