The secretory response to cholinergic stimulation was investigated in rectal biopsy specimens from children with cystic fibrosis and a control group using a modified Ussing chamber technique. Acetylcholine (10(-3) mol/l) increased the short circuit current in 12 control specimens by mean (SEM) 83.0 (16.4) microA/cm2, but samples from five children with cystic fibrosis failed to exhibit such a response (-1.4 (3.2) microA/cm2). Amiloride (10(-4) mol/l), which will inhibit electrogenic sodium absorption in viable tissues, caused similar reductions in the short circuit current of both control and cystic fibrosis tissues (control = -37.7 (7.7) microA/cm2; cystic fibrosis = -44.0 (9.3) microA/cm2). Thus, the failure of chloride secretion observed in the small intestine also exists in the rectal mucosa. This observation could be used both to aid diagnosis and to study the basic defect.