The secretory activity of jejunal biopsies from children with cystic fibrosis (CF) has been investigated using a modified Ussing chamber technique. Samples from six children with CF failed to respond when challenged with the intestinal secretagogues acetylcholine (10(-3) M), prostaglandin E2 (1.4 X 10(-6) M) and dibutyryl cyclic AMP (10(-3) M), while control tissues exhibited rises in short circuit current of 28.1 (7.4) (6) microA/cm2, 23.4 (4.6) (6) microA/cm2 and 10.0 (2.0) (4) microA/cm2 respectively in response to these agents. The calcium ionophore, A23187 (3.8 X 10(-6) M), increased the short circuit current in all the control tissues (mean change = 10.1 (2.7) (5) microA/cm2) and induced a small response in some of the CF tissues. Both groups of tissues generated a rise in short circuit current associated with sodium linked glucose (10 mM/l) absorption (control = 32.6 (9.3) (6) microA/cm2, CF = 36.2 (13.9) (6) microA/cm2, p greater than 0.05). These results show that the defect in chloride transport observed in other epithelia in CF also exists in the jejunum and could contribute to the intestinal effects of the disease. The technique used should permit further studies of the basic defect and may be of diagnostic value.