1. The renal function changes induced by dietary protein are thought to result from the activity of hormonal factors that remain as yet undefined. Since a meat meal and high dose atrial natriuretic factor (ANF) infusions have similar effects on glomerular filtration rate, natriuresis and kaliuresis, we decided to investigate the possibility that a protein meal could stimulate ANF activity. 2. We studied 10 normal volunteers who had a fixed protein and sodium intake for 7 days before the experiments. The subjects received a meat meal (1-1.5 g of protein/kg) and, on a separate occasion, a carbohydrate meal that had a similar caloric, sodium and potassium content. Diuresis was stimulated with water ingestion, and urine collections were obtained before the meals (baseline) and after the meals for a period of 3 h. Blood samples were obtained 30 min and 5 min before the meals and every hour for 3 h in the period after the meal. 3. The protein meal, but not the carbohydrate meal, was associated with parallel increments in plasma immunoreactive ANF (i-ANF), natriuresis, kaliuresis and glomerular filtration rate (estimated from creatinine clearances) which reached peak values 2-3 h after the meal. The mean increment of plasma i-ANF after the protein meal represented a twofold increase over baseline levels. 4. We conclude that ANF may participate in the physiological response to an oral protein load.