To the Editor: I write to comment on and to question features of the recent publication from Dessi-Fulgheri and colleagues that appeared in the February issue of Hypertension ( Hypertension . 1999:33;658–662). The authors report that a bolus injection of ANP produces greater falls in blood pressure, greater increases in plasma cyclic GMP, and a greater suppression of plasma aldosterone that are all accompanied by increased natriuresis in obese subjects who have had a low-calorie diet for 4 days as compared with the response to ANP prior to calorie restriction. Several difficulties arise with this report. First, the dose employed is unclear. The abstract employs 0.6 mg/kg. In “Results,” a dose of 0.6 μg/kg is reported, and then in “Discussion,” 0.6 mg/kg reappears. This 1000-fold difference in dose should be of some concern. Notably, even 0.6 μg/kg (over 50 μg as a bolus) is a large dose and cannot be considered as ranking among “low doses” as these authors suggest. A bolus injection of this dose will produce pharmacological levels of plasma ANP never reproduced in health or in any pathophysiological state. Certainly such an injection will not result in “changes in circulating ANP confined within the normal range” as these authors claim. This information was well established by the mid-1980s when it became clear that the plasma half-life of human ANP was a little under 3 minutes. Early reports from our group indicated that a 100-μg bolus resulted in plasma ANP levels in excess of 2500 pmol/L at 1 minute after intravenous injection, with an exponential fall in levels over the first 10 minutes, and a return …