We compared hemodynamics, ventricular function, and force-frequency relationships in six open-chest and six closed-chest anesthetized mice (FVB/N strain). Left ventricular (LV) pressure was measured with a 1.8- or 1.4-Fr Millar catheter placed via the right carotid artery and the LV apex in the closed-and open-chest state, respectively. Pacing was performed with electrodes placed either directly on atrial appendages (open chest) or with a l-Fr bipolar catheter via the jugular vein (closed chest). Closed-chest animals had greater spontaneous heart rate (267 +/- 106 vs. 147 +/- 27 beats/min), LV systolic (81 +/- 14 vs. 48 +/- 9 mmHg) and diastolic pressures (11.2 +/- 4.8 vs. 5.6 +/- 2.4 mmHg), and maximal rise (+dP/dt(max): 6,208 +/- 2,519 vs. 3,682 +/- 671 mmHg/s) and fall in pressure development (-dP/dt(max): -6,094 +/- 2,386 vs. -3,001 +/- 399 mmHg/s). LV systolic pressure (98 +/- 18 vs. 52 +/- 11 mmHg), +dP/dt(max) (9,240 +/- 2,459 vs. 5,777 +/- 2,473 mmHg/s), and -dP/dt(max) (-8,375 +/- 2,551 vs. -3,753 +/- 1,170 mmHg/s) were significantly higher when animals were matched at a heart rate of 420 beats/min in closed-chest vs. open-chest animals. Biphasic force-frequency relationships were seen in all animals, but the critical heart rate was greater in the closed-than open-chest animals (432 +/- 42 vs. 318 +/- 42 beats/min). We conclude that 1) there are significant differences between invasive indexes of systolic and diastolic function between the closed- and open-chest preparations, 2) there is a biphasic force-frequency relationship in the anesthetized mouse, and 3) dP/dt(max) can be used to assess the cardiovascular phenotype.