Sequence similarities are detected between human epidermal growth factor-urogastrone, human pancreatic secretory trypsin inhibitor, and members of the secretin family of gastrointestinal hormones, particularly gastric inhibitory peptide. These similarities suggest a common evolutionary origin for these proteins and a possible functional relationship, as evidenced by the ability of human epidermal growth factor-urogastrone and human pancreatic secretory trypsin inhibitor to form a complex with protease and the ability of human epidermal growth factor-urogastrone and secretin family members to inhibit gastric acid secretion.