OBJECTIVE To investigate the role of nitric oxide (NO) in the pathogenesis of asthma, we observed the influence of L-NG-arginine-methylester (L-NAME), the inhibitor of nitric oxide synthase (NOS), on the contraction of isolated guinea pig tracheal smooth muscles and observed the changes of NOS in the guinea pig asthma model lung tissues using histochemical detection. METHODS Male Hartley guinea pig isolated tracheal ring were incubated with L-NAME 2.0 mmol/L for 30 min and histamine was given to make a concentration response curve. The sections of guinea pig asthma model lung tissues were stained with NADPH diaphorase. RESULTS The histamine concentration response curve was significantly shifted upward in the L-NAME incubated group, the maximal response increased by 170% compared with that of control group. The numbers of alveolar macrophages were significantly increased and NADPH diaphorase staining was positive in asthma model group, in contrast, the alveolar macrophages were hardly seen and there was almost no positive staining of NOS in the control group. CONCLUSIONS The inhibition of NO synthesis of guinea pig respiratory tract with L-NAME results in a marked increase in airway contraction in vitro after histamine provocation. This result indicate that NO has relaxant effect on tracheal smooth muscles and may decrease airway responsiveness to histamine. The increased alveolar macrophages and positive stained NOS in the lung tissues of asthma model indicate that NO, which is synthesized by the NOS in alveolar macrophages, may play an important role in asthma pathogenesis.