It has been previously established that hyperthyroid myocardium exhibits increased performance under well-oxygenated conditions. To date, it is not known whether hyperthyroid cardiac muscle can maintain this increased performance during hypoxia. The responses of isolated right ventricular papillary muscles from hyperthyroid and euthyroid kittens to hypoxia were compared under isometric conditions at 31 degrees C. Under well-oxygenated conditions, the hyperthyroid cardiac muscle exhibited both an increased contractility and an accelerated rate of relaxation. A similar degree of acute hypoxic stress for 15 min resulted in a greater decrease in contractility in the hyperthyroid compared with the euthyroid papillary muscle as indicated by a greater fall in both peak tension development (2.2 +/- 0.25 from 4.2 +/- 0.2 vs. 0.9 +/- 0.15 from 3.2 +/- 0.4 g/mm2, P less than 0.01) and +dT/dt (12.9 +/- 2.3 from 25 +/- 3 vs. 4.0 +/- 0.6 from 14 +/- 1 g-s-1-mm-2, P less than 0.01). In addition, compared with the euthyroid data, hypoxia resulted in impaired myocardial relaxation in the hyperthyroid cardiac muscle. Thus, the hyperthyroid compared with the euthyroid papillary muscle exhibits both a greater decrease in contractility and an impairment of myocardial relaxation during hypoxia, indicating a greater susceptibility to a given hypoxic stress.