Nucleotides can be released as signaling substances in the nervous system from both neural and glial cells. Their function is terminated by ecto-nucleotidases and sequential extracellular metabolism to the nucleoside. Recently considerable progress has been made in unraveling the molecular structure of an ecto-ATPase and an ecto-ATP diphosphohydrolase, two closely related ecto-enzymes. Molecular structure, tissue distribution and functional properties of the ecto-nucleotidases are discussed with particular emphasis on the nervous system. © 1998 Elsevier Science Ltd. All rights reserved.