The effect of ketamine (105and 104M) on the intrinsic contractility of left ventricular papillary muscle from normal hamsters and those with cardiomyopathy (BIO 82.62, 6-month old) was investigated. At these concentrations, ketamine induced a positive inotropic effect on normal papillary muscle, as shown by an increase in maximum unloaded shortening velocity (+19 ± 4 and +34 ± 5%,P< 0.05), active isometric force (+32 ± 8 and +57 ± 11%,P< 0.05), and peak power output (+40 ± 8 and +80 + 16%,P< 0.05), and induced a slight decrease in sarcoplasmic reticulum function. Ketamine had no effect on the curvature of the total force-velocity curve, suggesting that it does not modify myothermal economy. Contractility of papillary muscle from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in isometric active force (-41%,P< 0.02), peak power output (-33%,P< 0.05), and sarcoplasmic reticulum function. The positive inotropic effect of ketamine on papillary muscle from hamsters with cardiomyopathy was less marked than in controls and almost suppressed in some cases: only the maximum unloaded shortening velocity was significantly increased with 10−5M ketamine (+7 ± 6%,P< 0.05), whereas no significant changes were observed in active isometric force (+14 ± 8 and +13 ± 11%; nonsignificant [NS]) and peak power output (+9 ± 5 and +13 ± 8%; NS) with ketamine (10−5and 10−4M, respectively). The effects of ketamine on contraction-relaxation coupling under low and heavy loads were similar to those observed with normal muscle. The direct mechanical effects of ketamine on cardiac muscle therefore depend on the pathophysiologic state; ketamine did not induce a significant inotropic effect on cardiomyopathy muscles.