Marcello Costa has produced a great deal of imaginative work over a period of over 20 years on the autonomic innervation of the gastrointestinal system. He has pioneered numerous histochemical methods and their application to define the neuronal architecture of the enteric nervous system. His studies of the neuronal reflexes underlying the patterns of motility of the intestine and his studies of the nature of the neurotransmitters involved has led to the discovery that not only acetylcholine but also the peptide substance P are excitatory neurotransmitters in the intestine and that there are at least two inhibitory transmitters. The combination of new methods applied in an imaginative and systematic way has greatly increased our knowledge of the enteric nervous system, making it one of the best understood parts of the mammalian nervous system. Some of the interrelationships observed in this system have provided clues of the function of central nervous system neurons.