The effect of simple and mixed copper(II) complexes of L-tryptophan (trp) and L-phenylalanine (phe) on the gastric acid secretion was investigated in Shay rats. Graded doses (from 15 to 75 mg/kg) of [Cu(trp)2(H2O)], [Cu(phe)2(H2O)] and [Cu(trp)(phe)(H2O)], administered i.g., caused a progressive inhibition of gastric acid secretion. The antisecretory activity of the mixed complex, [Cu(trp)(phe)(H2O)], was significantly greater (ID50 = 33 +/- 3 mg/kg) than that of the simple complexes [Cu(trp)2(H2O)] (ID50 = 48 +/- 3 mg/kg) and [Cu(phe)2(H2O)] (ID50 = 43 +/- 3 mg/kg). At the experimental conditions of intragastric pH, the different biological activities were directly related to the percentage of neutral species present in solution as determined by means of potentiometric measurements (at 37 degrees, I = 0.15 mol dm-3 in NaClO4). A possible mechanism of action of the investigated compounds is discussed.