This symposium focuses on recent developments in the cellular and molecular basis of myocardial contractility. This topic is an essential element in modern exercise biology as both the acute and chronic responses to exercise are dependent on these mechanisms. The papers in this symposium reflect knowledge garnered from advances over the past decade in a variety of fields including: molecular biology, tissue culture (isolation of functional myocytes), organic chemistry (fluorescent Ca2+ indicators), and electrophysiology (patch clamp technology). In cardiac muscle, contractility is regulated essentially in two ways: the intracellular Ca2+ transient and the response of the myofilaments to that transient. This symposium addresses both of these mechanisms in some detail. The response of the myofilaments can be altered through both covalent modification (e.g., phosphorylation) of various contractile proteins and noncovalent (e.g., change in pH) mechanisms. The [Ca2+]i can increase from about 100 nM in diastole to the low microM range in systole. The peak [Ca2+]i observed in systole can vary several-fold owing to an orchestrated modulation of several different Ca2+ transport proteins on both the sarcolemma and sarcoplasmic reticulum. This modulation is quite distinct from that observed in skeletal muscles and underscores the physiological differences in these two types of striated muscle in varying contractile force. These proteins include: the L-type voltage-dependent Ca2+ channel and the Na+/Ca2+ exchanger in the sarcolemma, and the Ca2+ release channel and Ca2+ pump in the sarcoplasmic reticulum. Each of these proteins is subject to complex regulation by a variety of modulators, and aspects of this regulation are discussed in detail.