The English physician E. H. Starling discovered in collaboration with the physiologist W. M. Bayliss secretin, the first hormone, in 1902. Three years later they introduced the hormone concept with recognition of chemical regulation, early regulatory physiology took a major step forward. The isolation and subsequent synthesis of secretin in the 1960s prepared the way for immunological techniques. Radioimmuno assays in the 1970s enabled demonstration of a direct endocrine role of secretin. Cloning and molecular hybridisation in the 1990s identified production site structure, precursor and evolutionary relation to other gastrointestinal peptides and to the secretin receptor. Although secretin was the first substance to be established as a hormone, even today our understanding is far from complete.