Immature hearts of various animal species and humans have been demonstrated to be more sensitive than adult hearts to the myocardial depressant effects of volatile anesthetics. To further investigate the mechanisms involved, the calcium sensitivity and maximal activated tension of detergent-treated left ventricular fibers of fetuses (30 days), newborn (1-day-old), immature (3-, 8-, and 17-day-old), and adult rabbits were determined by stepwise exposure to increasing Ca2+concentrations. Responses were measured prior to and after exposure to equianesthetic concentrations of halothane (1%) or isoflurane (1.5%) applied in a random order. In control conditions maximal developed tension was the lowest in fetuses (11.1 ± 0.6 mN · mm-2), intermediate in newborn and immature rabbits, and highest in adults (25.6 ± 2.9 mN · mm-2). There were also age-related changes in calcium sensitivity; pCa (= -log10[Ca2+]) for half-activation (pCa50) was significantly less in 1-, 3-, and 8-day-old rabbits (5.444 ± 0.036, 5.425 ± 0.017, and 5.385 ± 0.019, respectively) than in adults (5.517 ± 0.010), whereas it was not different in fetuses (5.521 ± 0.017). During anesthetic exposure both calcium sensitivity and maximal developed tension decreased significantly in all age groups of animals, with both anesthetics having a similar effect in animals of identical age. However, calcium sensitivity decreased significantly more in newborn animals (0.192 and 0.196 pCa unit for halothane and isoflurane, respectively) compared with adults (0.122 and 0.137 pCa units, respectively). By contrast, fetuses were less sensitive to the myocardial depressant effects of anesthetics than were newborn animals. The results of this study are consistent with the hypothesis of a greater sensitivity of contractile apparatus of neonatal heart to the depressant effects of volatile anesthetics. This could be related to developmental changes that are known to affect the contractile proteins, especially the troponin-tropomyosin system.