The pattern of asthmatic response after inhalation of atropine and methacholine was studied in six adult asthmatics. After pretreatment with atropine, the provocation concentration of methacholine to cause a fall in FEV1 of 20% was increased from 0.66 +/- 2.09 to 94.90 +/- 1.78 mg/ml. In the subsequent 7 hr, four subjects developed prolonged asthmatic responses. These occurred after concentrations of methacholine higher than those used clinically but did not directly relate to the dose of methacholine or to the increase in dose after atropine. In one subject the prolonged response was not accompanied by increased methacholine responsiveness and was not prevented by pretreatment with cromolyn sodium (40 mg). These results show that high doses of methacholine inhaled after pretreatment with atropine can induce prolonged asthmatic responses but the mechanism is unclear.