The effect of pretreatment with nifedipine 20 mg sublingually on the bronchoconstrictor response to inhaled histamine and methacholine in asthmatic and normal subjects has been studied. For each agonist the provocation concentration required to produce a 15% fall in FEV1 (PC15) and a 35% fall in specific conductance (PC35) was determined. In the group of asthmatic subjects the responses to histamine were significantly attenuated by histamine, PC15 increasing from 0.29 mg/ml to 0.68 mg/ml (P less than 0.001) and PC35 increasing from 0.25 mg/ml to 0.58 mg/ml (P less than 0.001). Responses to methacholine showed less modification by nifedipine. PC15 increased from 0.23 mg/ml to 0.32 mg/ml (P less than 0.05). Changes in PC35 were not significant. In the group of normal subjects no attenuation of the response to methacholine was produced by nifedipine but significant increases of PC15 (P less than 0.002) and PC35 (P less than 0.005) were produced by the agent. The results are consistent with nifedipine exerting an effect principally on mediators dependent on external calcium sources for stimulus-contraction coupling in the airways. The magnitude of change in the histamine response of the two groups was similar, suggesting calcium dependent mechanisms are not involved in asthmatic hyper-responsiveness.