Recombinant human interleukin-11 (rhIL-11), or Neumega rhIL-11 Growth Factor, is a recombinant cytokine that stimulates megakaryocytopoiesis, increases platelet production, and also has shown anti-inflammatory and immune-modulating activity. Mild, reversible anemia was the most common adverse event observed in clinical studies and was demonstrated to be related to hemodilution. The purpose of this study was to examine the renal mechanisms of the rhIL-11-induced volume retention and devise a possible therapeutic intervention to ameliorate this effect. Eighteen healthy volunteers (9 male and 9 female) on a controlled sodium (180 mEq/day) and potassium (120 mEq/day) diet were randomized to one of six treatment sequences in a three-period crossover design. Each subject received 25 micrograms/kg IL-11 s.c. once daily, 25 micrograms/kg IL-11 s.c. once daily + Maxzide-25 twice daily, or placebo for 7 days in a crossover design. There was a 14-day washout period between treatment periods. Renal clearance parameters indicated that mean sodium excretion was decreased compared to placebo within 8 hours after dosing with rhIL-11, with these results reaching statistical significance 8 to 16 hours postdose (p < 0.01). The cumulative sodium excretion (mEq +/- SD) over the 7-day treatment period for each respective treatment group was the following: rhIL-11 = 833 +/- 154, rhIL-11 + Maxzide-25 twice daily = 1114 +/- 178, and placebo = 982 +/- 193 (p < 0.01). Hemoglobin concentration and hematocrit values, used as indicators of hemodilution, decreased in the rhIL-11-treated group as compared to the baseline and placebo groups (p < 0.01). Concurrent dosing with Maxzide-25 twice daily reduced the rhIL-11-associated hemodilution by about 50%.