METHACHOLINE CHLORIDE IS THE ?-METHYL HOMOLOG OF ACETYLCHOLINE AND DIFFERS FROM THE LATTER PRIMARILY IN ITS GREATER DURATION AND SELECTIVITY OF ACTION. BRONCHIAL SMOOTH MUSCLE CONTAINS SIGNIFICANT PARASYMPATHETIC (CHOLINERGIC) INNERVATION. WHEN A SODIUM CHLORIDE SOLUTION CONTAINING METHACHOLINE CHLORIDE IS INHALED, SUBJECTS WITH ASTHMA ARE MARKEDLY MORE SENSITIVE TO METHACHOLINE-INDUCED BRONCHOCONSTRICTION THAN ARE HEALTHY SUBJECTS. THIS DIFFERENCE IN RESPONSE IS THE PHARMACOLOGIC BASIS FOR THE PROVOCHOLINE METHACHOLINE CHLORIDE. METHACHOLINE CHALLENGE MAY OCCASIONALLY BE POSITIVE AFTER INFLUENZA, UPPER RESPIRATORY INFECTIONS OR IMMUNIZATIONS, IN VERY YOUNG OR VERY OLD PATIENTS, OR IN PATIENTS WITH CHRONIC LUNG DISEASE (CYSTIC FIBROSIS, SARCOIDOSIS, TUBERCULOSIS, CHRONIC OBSTRUCTIVE PULMONARY DISEASE). THE CHALLENGE MAY ALSO BE POSITIVE IN PATIENTS WITH ALLERGIC RHINITIS WITHOUT ASTHMA, IN SMOKERS, IN PATIENTS AFTER EXPOSURE TO AIR POLLUTANTS, OR IN PATIENTS WHO HAVE HAD OR WIL IN THE FUTURE DEVELOP ASTHMA.