Abstract The gastric inhibitory activity of somatostatin analogues modified in position 4 or 9, was investigated in conscious cats prepared with gastric fistulae. Gastric secretion was stimulated with pentagastrin. Deletion of Lys 4, or substitution with an alcoholic (Thr) or acidic (Glu) residue yielded analogues with reduced (10% or less) potency compared with somatostatin. In comparison, [Phe 4]somatostatin and modified Phe 4 analogues ([p-NH 2-Phe 4]-, [F 5Phe 4]- and [Phe 4, d-Trp 8]somatostatin) were approximately equipotent with somatostatin. The high potency of the Phe 4 analogues illustrates that a basic side-chain in position 4 is not essential for gastric activity. In contrast, [Thr 9]-, [Glu 9]-, [Phe 9]- and [p-NH 2-Phe 9]somatostatin were all inactive (< 5% potency of somatostatin) in the stomach. Thus the lysyl residue in position 9 is more critical than that in position 4 for somatostatin's gastric activity.