Airway smooth muscle preparations were isolated from control guinea pigs, from animals sensitized to albumin and Pertussis vaccine, from sensitized animals which had been resensitized and from animals that had been sensitized and exposed to an inhalation challenge of albumin for 14 days. The resting membrane potential, its changes and contractile response of airway smooth muscle were measured during in vitro antigen challenge, administration of histamine dihydrochloride (10(-3) M), or isoproterenol (10(-3) M). We have found that: (1) The resting membrane potential of normal airway smooth muscle of guinea pig was -61.3 +/- 0.2 mV (+/- SE); (2) Resting membrane potential of airway smooth muscle from sensitized animals was significantly increased (P less than 0.05) to -72.9 +/- 0.3 mV (+/- SE); (3) One week after resensitization of animals a further significant increase (P less than 0.05) in resting membrane potential to -76.2 +/- 0.2 mV (+/- SE) was observed; (4) Resting membrane potential of airway smooth muscle isolated from animals repeatedly exposed to inhalation challenge of antigen significantly decreased (P less than 0.01) to -50.6 +/- 0.5 mV (+/- SE) as compared to controls; (5) After histamine, isoproterenol or antigen administration, the airway smooth muscle from sensitized animals repeatedly exposed to inhalation challenge showed attenuated response (P less than 0.01) as measured by both membrane potential and isometric force. In contrast, the response to antigen and histamine in preparations from sensitized animals is potentiated. It is concluded that both acute sensitization and resensitization on one hand and repeated exposure of sensitized animals to inhaled albumin on the other will alter cellular mechanism(s) responsible for the maintenance of membrane potential and the regulation of excitation-contraction coupling in airway smooth muscle.