Respiratory epithelium modulates airway smooth muscle reactivity by releasing epithelium-derived relaxing factor (EpDRF). We studied earlier the relationship between epithelial bioelectric events and EpDRF release. Here we describe a method for simultaneous evaluation of airway diameter (estimated from inlet - outlet pressure difference, P) and bioelectric properties including transepithelial potential difference (Vt) and resistance (Rt). Rt was derived from changes in Vt induced by transmural current pulses (20 :A, 5 s duration, 50 s intervals). Basal Vt, was 14.8 +/- 0.8 mV. Histamine (7.4 :M) and terbutaline (0.1 :M) caused contraction and relaxation, respectively, but no change in Tt and Rt when added to the extraluminal (EL) bath. The Na, K-pump inhibitor, ouabain (10 :M, EL), caused contraction, depolarization and decreased Rt. The Na-K-2C1 cotransporter inhibitor, bumetanide (10 :M, EL), caused relaxation, depolarization and no change in Rt. Amiloride (30 :M, IL), a Na channel blocker, and NPPB (100 :M, IL) a C1 channel blocker, evoked depolarization without changing P. Amiloride also increased Rt. Elevation of IL osmolarity (300 mosM) with NaCl or D-mannitol elicited depolarization and EpDRF-mediated relaxation. NaCl decreased, but D-mannitol increased, Rt. This apparatus should be useful for studying interaction between the airway epithelium and smooth muscle.