The leukotrienes LTC₄, D₄, and E₄ are potent bronchoconstrictor agents and are thought to have an important role in asthma. Urinary LTE₄, a stable urinary end-product of LTC₄ and LTD₄, was measured, by means of high-performance liquid chromatography and radioimmunoassay. LTE₄ excretion followed a log-normal distribution in twenty-nine healthy controls, with a geometric mean of 23·8 (95% confidence interval 19·9-28·2) ng/mmol creatinine. Urine was collected from eight atopic subjects for 3 h after antigen inhalation and a control urine collection was made a week later at the same time of day. Urinary LTE₄ was significantly higher after antigen challenge than in the control sample (153·7 [87-1-271·3] vs 23·5 [13·7-69·5] ng/mmol creatinine; p<0·01). Urinary LTE₄ was also measured in twenty patients with severe acute asthma and nine patients with seasonal allergic rhinitis. Mean urinary LTE₄ was higher in the asthmatic patients (78·3 [46·5-131·8] ng/mmol creatinine) than in normal subjects (p<0·01), although there was substantial overlap into the normal range. The urinary LTE₄ values of the rhinitis patients were within the normal range whether or not they had symptoms. LTC₄ and LTD₄ were also found in bronchoalveolar lavage fluid from one of the three atopic subjects challenged with antigen before lavage, and in Professor of Medicine, Royal Postgraduate Medical School. a single patient who underwent lavage after admission with severe acute asthma. These studies provide evidence that leukotrienes are released in vivo in man after antigen challenge and in acute asthma.