Basic research into cystic fibrosis (CF) has been hampered by the lack of a suitable animal model. Reserpinized or isoproterenol-treated rats have been proposed as models because they exhibit certain morphological and physiological features characteristic of CF. Recent evidence suggests that abnormal epithelial transport of Na+ [corrected] and Cl- may underlie pathogenesis, defects that may contribute to the markedly more negative transepithelial electrical potential differences (PD) recorded in CF airways compared with controls. To test the models further, we measured tracheal PD in vivo in treated rats (reserpinized - 6.9 mV, SEM 0.7 mV, n = 7; isoproterenol-treated -10.2 mV, SEM 1.5 mV, n = 12) and found it to be no different from that of controls (-8.7 mV, SEM 0.6 mV, n = 25). The animals did, however, demonstrate a reduced gain in body weight as well as increased submaxillary gland weight, which reflected an increased mucus content in the acini. These observations suggest that although the reserpinized or isoproterenol-treated rat may be useful in the study of the pathogenesis of exocrine disturbances in disease, their use as models for the effect of the basic defect of CF in the airways may be limited.