DDAVP-related hyponatremia induces a blood volume expansion, but the analysis of fluid distribution in the vascular compartment has given controversial results in previous animal and human studies. In 5 healthy males, hyponatremia was induced by DDAVP and a free water intake during 3 days. Serum sodium concentration decreased from 138 +/- 0.8 mEq/L to 123 +/- 2.7 mEq/L on day 3. The plasma volume measured by dilution of marked albumin rose from 3033 +/- 230 ml to 3320 +/- 295 ml (p < 0.01). The mean corpuscular volume measured by microhematocrit increased slightly from 91.5 +/- 3.8 pl to 92.6 +/- 3.7 pl (p < 0.02). The red blood cell volume calculated with hematocrit and plasma volume did not change significantly (2565 ml to 2567 ml; not significant). In the present work, we demonstrated that in males the expansion of the plasma compartment almost completely amounted for the water retention in the intravascular volume. The erythrocyte volume increased only slightly, a finding that is consistent with an almost perfect adaptation of the erythrocyte cells to the hypoosmolality.