1. The influence of previous mechanical events on myocardial contractility has been investigated in the cat papillary muscle preparation.2. When a muscle that had been producing a stable response under isometric conditions was allowed to shorten isotonically, its ability to do so increased in successive beats until it reached a steady level, which represented a potentiated state compared with that seen in the first isotonic beat and in the preceding stable isometric contractions.3. The increase in tension development in the first isometric beat after a period of isotonic beating was used as an index of the degree of potentiation. It was found to be well correlated with the changes in other parameters that could have been used for this purpose.4. The main determinants of the degree of potentiation produced by a period of isotonic beating were:(a) the amount by which the muscle shortened. This was inversely related to the force opposing shortening (i.e. the isotonic load);(b) the number of isotonic beats. There was some potentiation (about 10%) after a single isotonic beat, but the number of beats required for maximal potentiation (up to 25%) depended on the frequency of stimulation; about 8 beats were required at 24 min(-1).5. An isotonic release during the rise of tension in an isometric response was even more effective in potentiating the next isometric beat than an afterloaded contraction against the same load. Isotonic releases at later times had a diminishing influence on tension development in the next isometric beat.6. In the absence of stimulation, the potentiated state produced by a period of isotonic beating decayed with a half-time of about 50 sec. When the muscle was stimulated it disappeared sooner, and its rate of decay depended on the frequency of stimulation; at 24 min(-1) about 8 beats were required to restore contractility to its previous steady level.7. The characteristics of the decay of the potentiated state were closely similar to those of the potentiated states that can be produced by various electrical interventions, and the possibility that all of these might have the same underlying mechanism is discussed.8. Attention is drawn to the practical implications of this phenomenon in the design of experiments in which the muscle contracts under changing mechanical conditions.