Calcium accumulation and storage by the sarcoplasmic reticulum is affected adversely by both inhaled anesthetics and hypertrophy. The interaction of these two conditions in right ventricular muscle was examined in a skinned fiber preparation whereby the sarcolemma was disrupted mechanically to permit external control of the chemical composition of the cytoplasm. Skinned fibers were obtained from the right ventricles of rabbits 4 mo after surgical banding of the pulmonary artery (n = 5) or sham banding (n = 4). Right ventricles after pulmonary artery banding weighed an average of twice that of normal right ventricles. The sarcoplasmic reticulum of the skinned fibers was permitted to accumulate Ca2+ and then maximal or submaximal Ca2+ release was induced with 25 mM or 2 mM caffeine, respectively. The magnitude of the Ca2+ release was estimated by the area of the ensuing tension over time. When 1%, 2%, or 3% halothane accompanied the 2 mM caffeine, both normal and hypertrophied muscle exhibited an area of the tension transient twice that of the tension transients without halothane (control). When present during Ca2+ accumulation, 1%, 2%, and 3% halothane reduced the 25 mM caffeine-induced tension transient in normal and hypertrophied muscle to 36%, 17%, and 11%, respectively, of the controls. The equal depression in normal and hypertrophied right ventricles was in contrast to a previous study in which hypertrophy provided some protection against the decrease in sarcoplasmic reticulum Ca2+ storage by halothane. The authors concluded that halothane enhances Ca2+ release from the sarcoplasmic reticulum in normal and hypertrophied right ventricular muscle in rabbits and that right ventricular hypertrophy did not protect against the marked inhibition by halothane of Ca2+ storage in sarcoplasmic reticulum.