Erythromycin, a commonly used antibiotic, has recently emerged as a potential gastrointestinal prokinetic agent. This follows a decade of research into the mechanism of well-recognized gastrointestinal side effects of erythromycin. Early investigations demonstrated that erythromycin increased gastrointestinal motility, and more recent studies suggest that it fortuitously binds to and stimulates the receptor for the gastrointestinal peptide motilin. From this work it appears that a new and powerful class of gastrointestinal prokinetic agents will evolve from erythromycin and its derivatives. The role of motilin in the genesis of the fasting and fed patterns of gastrointestinal motility is emerging through the study of these motilin agonists.