The effect on guinea pig airways of the inhalation of leukotrienes, histamine or antigen was investigated by measuring changes in lung volume and analyzing the airway area on bronchograms with the Zeiss interactive image analysis system (IBAS). LTC4, LTD4, LTE4 and histamine inhaled through an ultrasonic nebulizer caused inflation of the lung: LTD4 was the most potent of the leukotrienes and was 100 times more potent than histamine on a molar basis. The results of analyses of areas of large and small bronchi and bronchioles on the bronchograms indicated that LTD4 selectively decreased the area of the peripheral airways. Inhalation of an antigen in actively sensitized animals resulted in inflation of the lung and in a selective decrease in the area of the peripheral airways. Anaphylactic bronchoconstriction provoked by antigen inhalation was clearly inhibited by AA-861, a 5-lipoxygenase inhibitor but not significantly by mepyramine, an antihistamine. These observations indicate that LTD4 is a potent constrictor of the peripheral airways in guinea pigs and that the anaphylactic bronchoconstriction provoked by antigen inhalation could be mediated by LTD4 in actively sensitized guinea pigs.