Adequate body and vocal fold hydration are believed to be critical to phonation. We hypothesized that body fluid reduction, without dehydration, would increase phonation threshold pressure (P(th)) and be associated with patient-perceived increases in phonatory effort and worsening voice quality. Using a single-subject, full-reversal design, a controlled volume of body fluid was repeatedly removed via ultrafiltration from adults with end stage renal disease (2 women, 4 men, ages 40-85 yrs). Two additional men (ages 81 and 68 yrs) served as placebo and healthy true controls, respectively. P(th), vocal effort and quality, blood pressure, and heart rate were assessed longitudinally. P(th) increased significantly with fluid volume reduction (3-4% of body weight from a hypervolemic to a grossly normovolemic body state) and reversed to baseline with fluid replacement in 4 of 6 treated subjects. Effects were observed with net ultrafiltration rates greater than or equal to 1.0 L/h; these effects were not observed in control subjects. Fluid loss accounted for 31.6% of variance in P(th) and 40.0% of variance in perceived vocal effort. Heart rate, systolic blood pressure, and/or diastolic blood pressure were significantly correlated with P(th) or fluid volume reduction in 6 subjects, including the placebo control (-.70 < or = r < or = -.44). Results indicate that substantial extracellular volume depletion without body dehydration causes voice symptoms, an effect possibly mediated by autonomic nervous control. We propose that mechanisms intrinsic to the vocal fold regulate its water flux and respond to hydration challenges.