It is not clear how contracting skeletal muscles mediate the numerous and diverse metabolic and physiological effects that are beneficial for health. Researchers have searched for a muscle-contraction-induced factor - an 'exercise factor' - that mediates some of the exercise effects in other tissues such as the liver and adipose tissue. In our search for such a factor, we encountered the cytokine interleukin (IL)-6, which is produced by contracting muscles and released into the blood. We propose that muscle-derived IL-6 meets the criteria of an exercise factor and that such classes of cytokine should be named 'myokines'. The discovery of contracting muscle as a cytokine-producing organ creates a new paradigm: skeletal muscle as an endocrine organ. By contracting, it stimulates the production and release of myokines that can influence metabolism in tissue and organs. Newly identified myokines and their receptors could serve as targets in the treatment of metabolic disorders and other diseases.