Protein intake-induced natriuresis previously related to increased urinary dopamine excretion was reexamined in an extensive controlled study comparing healthy and hypertensive subjects. In healthy subjects, ingestion of 1 g/kg wt tuna induced natriuresis that was associated, between postprandial hours 1 and 2, with increased plasma tyrosine [191 ± 13% (mean ± SE); P < 0.01], 3,4-dihydroxyphenylalanine (104 ± 12%, P < 0.05 in plasma; 162 ± 20%, P < 0.05 in urine), plasma free dopamine (156 ± 32%; P < 0.05), and dopamine sulfate (191 ± 11%, P < 0.001 in plasma; 199 ± 15%, P < 0.01 in urine) but affected urinary free dopamine excretion only at limits of significance. Hypertensive subjects had less (P < 0.02) natriuresis and, despite comparable plasma tyrosine and dopamine sulfate increases, no increase in plasma and urinary 3,4-dihydroxyphenylalanine and plasma free dopamine. Their plasma and urinary free epinephrine responses were less (P < 0.05) than the borderline increases in control subjects. Compared with control subjects, they significantly increased plasma 3,4-dihydroxyphenylalanine sulfate (P < 0.05), epinephrine sulfate (P < 0.05), and the dopamine sulfate-to-free dopamine ratio (P < 0.02). Postprotein natriuresis is thus associated with nutritional priming-induced plasma but not urinary free dopamine increase. Hypertensive subjects have attenuated natriuretic and plasma free dopamine responses and less free epinephrine increase. This may partly result from higher circulating 3,4-dihydroxyphenylalanine, dopamine, and epinephrine sulfoconjugates leaving fewer free amines for biological actions.