Eight left ventricular papillary muscles were removed from patients at the time of mitral valve replacement (all patients functional class 3 to 4) and were studied in a myograph in vitro to determine their relative responsiveness to various inotropic agents. Results were compared with 7 dog and 9 cat papillary muscles studied under the same conditions. Maximum dp/dt of an isometric contraction at Lmax was used as an index of contractile state. The ratios of the response to 10<sup>-5</sup> M glucagon and 10<sup>-5</sup> M isuprel (G/I) and to glucagon and paired stimulation (G/PS), were used as indices of glucagon responsiveness. In the human muscles, G/I = 0.03 ± 0.01, G/PS = 0.07 ± 0.02; for the dog papillary muscles. G/I = 0.40 ± 0.08, G/PS = 0.34 ± 0.05; and for the cat papillary muscles, G/I = 0.29 ± 0.05, G/PS = 0.28 ± 0.05. Although no data is available from normal human papillary muscles, the present data suggests that the failing human myocardium has a reduced inotropic response to glucagon.