Previously we demonstrated that intact female rats fed a standard rodent diet containing soybean products exhibit essentially no adverse left ventricular (LV) remodeling in response to aortocaval (AV) fistula-induced chronic volume overload. We hypothesized that phytoestrogenic compounds in the diet contributed to the female cardioprotection. To test this hypothesis, four groups of female rats were studied: sham-operated (SHAM) and AV fistula (FIST) rats fed a diet with (P(+)) or without (P(-)) phytoestrogens. Eight weeks post-fistula, systolic and diastolic cardiac function was assessed using a blood-perfused isolated heart preparation. High phytoestrogen diet had no effect on body, heart and lung weights, or cardiac function in SHAM rats. Fistula groups developed LV hypertrophy, which was not reduced by dietary phytoestrogens (1184±229 mg FIST-P(-) and 1079±199 mg FIST-P(+) vs. 620±47 mg for combined SHAM groups, p<0.05). Unstressed LV volume increased in FIST-P(-) rats (428±16 µl vs. 300±14 µl SHAM, p<0.0001), but was not different from SHAM for FIST-P(+) animals (286±17 µl). Also, FIST-P(-) rats developed increased ventricular compliance (5.3±0.8 µl/mmHg vs. 2.3±0.3 µl/mmHg SHAM, p<0.01), whereas FIST-P(+) rats had no significant change in compliance (2.8±0.4 µl/mmHg). Intrinsic ventricular contractility was maintained in the FIST-P(+) rats, but was significantly reduced (p<0.001) in the FIST-P(-) rats (slope of systolic pressure-volume relation: 1.06±0.04, 0.60±0.06, and 0.99±0.08 mmHg/µl, FIST-P(+), FIST-P(-) and SHAM respectively). These data indicate that dietary phytoestrogens contribute significantly to female cardioprotection against volume overload-induced adverse ventricular remodeling, and that future studies evaluating gender differences in cardiovascular remodeling must consider the influence of dietary phytoestrogens.