Antagonists and synthesis inhibitors of several proposed mediators in asthma have been investigated in humans. Drugs blocking histamine, thromboxane A2, and platelet-activating factor have either shown no activity or their activity has been too limited to be of clinical relevance. In contrast, for drugs affecting the leukotriene pathway, there is now extensive evidence demonstrating clinically important effects in preventing antigen- and exercise-induced asthma and clinical asthma. In short- and long-term placebo-controlled studies, potent leukotriene antagonists, such as zafirlukast (Accolate(TM), ICI-204,219), have been shown to improve lung function and symptoms and to reduce the use of β2-agonists in mild to moderately severe asthma. These effects can be seen within a few hours of dosing. In some studies, these beneficial effects are additional to those seen with inhaled steroids and β2-agonists, and recent data suggest an effect in preventing exacerbations of asthma. The studies available at present have demonstrated the efficacy of antileukotriene drugs in patients whose symptoms are not well controlled with β2-agonists and in preventing antigen- and exercise-induced asthma. Further studies in children and comparisons with established therapy, such as inhaled glucocorticosteroids, are now required to establish the place of leukotriene receptor antagonists and synthesis inhibitors in asthma treatment guidelines.