Because the physiologic significance of the presence of the opioid peptides beta-casomorphins (beta-CMs) in enzymatic digestion of milk proteins is still undetermined, the effect of the nonmetabolized beta-CM analogue beta-[DAla2,4,Tyr5]CM-5-NH2 on water and electrolyte movements was studied in vivo and in vitro in rabbit ileum untreated or treated with cholera toxin (CT). When this analogue was introduced in vivo at a concentration of 10(-3) M into the lumen of rabbit ileal loops, it significantly stimulated net water absorption in untreated loops and reduced net water secretion in CT-treated loops. In vitro addition of this analogue (10(-4) M) to the serosal compartment of untreated ileum in an Ussing chamber reduced Isc (delta Isc = 0.44 +/- 0.05 muEq.h-1/cm2) and stimulated net Na and Cl absorption to the same extent. In CT-treated ileum, both serosal (10(-4) M) and mucosal (5.10(-4) M) addition of the analogue did not further modify the rise in Isc caused by CT but also stimulated net Na and Cl absorption. On the mucosal side, the effect of the analogue was accompanied by its transfer from the luminal to the blood side of the tissue. The transferred analogue was intact as shown by HPLC (Jm----s = 2.4 +/- 0.8 nmol.h-1/cm2). These results demonstrated that the beta-CM analogue stimulates intestinal absorption of electrolytes in rabbit ileum both in the basal state and after its stimulation by CT.(ABSTRACT TRUNCATED AT 250 WORDS)