The effects of acute and chronic exercise on 3'5'-adenosine monophosphate (cAMP) concentration, adenylate cyclase activity, cAMP-phosphodiesterase (PDE), and cAMP-dependent protein kinase (A-kinase) activity are reviewed. During very mild- to moderate-intensity exercise with durations of up to 1 h, the cAMP concentration within the myocardium is related to the intensity of exercise. At higher intensities or during very long-duration exercise, this does not seem to be the case. The mode of exercise does not seem to be a significant factor in altering cardiac cAMP concentration. Duration is more important than intensity in determining cAMP-PDE activity. Post-exercise increases in cAMP-PDE are very similar in trained animals, independent of duration and intensity of work. These increases are attenuated and less variable as compared with untrained animals. The activity of A-kinase seems to increase with exercise training. The extent of the increase in A-kinase activity is likely dependent on the duration (and perhaps the intensity) of training and is of greater magnitude than the changes in the other enzymes of the cAMP system.