Background: A reduced central blood volume is reflected by a decrease in mid-regional plasma pro-atrial natriuretic peptide (MR-proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head-down tilt (HDT). We determined plasma MR-proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account. Methods: Patients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR-proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10^° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered. Results: Plasma MR-proANP decreased for patients undergoing gastroesophageal surgery (−9% [95% CI −3.2 to −15.3], p =.004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR-proANP and fluid balance were correlated (r =.352 [95% CI 0.031–0.674], p <.001). In contrast, plasma MR-proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR-proANP and fluid balance, and no patient was fluid responsive. Conclusion: Plasma MR-proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.