The cardiovascular responses associated with isovolemic hemodilution have been described. However, the stability of these responses over time remains controversial. We hypothesized that the hemodynamic responses to isovolemic hemodilution are stable over time. Nine fentanyl-midazolam-anesthetized dogs were monitored to follow global cardiovascular and regional myocardial function. Isovolemic hemodilution was performed to a moderate (hemoglobin = 7.5 g%) target hemodilutional state that was maintained for 4 h. Data were obtained at each hemodilutional state and each hour during the 4-h period of sustained moderate hemodilution. During acute hemodilution, cardiac output increased from 2.6 +/- 0.5 L/min to 3.0 +/- 0.5 L/min (P < 0.05) and mean coronary flow increased from 20.8 +/- 2.4 mL/min to 31.4 +/- 5.5 mL/min (P < 0.05). Cardiac output and mean coronary flow remained elevated during the extended hemodilutional period. In addition, norepinephrine increased from 586 +/- 152 pg/mL to 1135 +/- 247 pg/mL (P < 0.05) during acute isovolemic hemodilution and remained at this increased level during extended hemodilution. Epinephrine levels did not change with hemodilution. Compensatory mechanisms such as increases in cardiac output and mean coronary flow observed during acute hemodilution persist during extended periods of hemodilution.