Prostaglandin E2 (PGE2) is produced in the lung but unlike most other lipid mediators has potentially important antiallergic effects. Whether these properties are relevant to asthma has not been established. The effect of inhaled PGE2 on allergen-induced asthma was examined in a double-blind crossover study of eight subjects with asthma. In Study 1 subjects inhaled 100 micrograms PGE2 or placebo 5 min before a normal saline challenge, and FEV1 and bronchial reactivity to methacholine was measured at intervals for 7 h. In Study 2, which had a similar design, subjects inhaled the same dose of PGE2 or placebo followed by a dose of allergen previously shown to cause a fall in FEV1 of 20% or more. On the normal saline challenge day inhaled PGE2 caused a small increase in FEV1 that lasted for around 60 min; there was no difference in the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) at 4 and 7 h compared with placebo. PGE2 caused marked inhibition of the early and late response to allergen. The mean maximum fall in FEV1 0 to 2 h after allergen was 37.8 and 7.7% with placebo and PGE2 pretreatment, respectively (mean difference 30%; 95% CI 15, 45%; p < 0.005). The mean maximum fall in FEV1 from 4 to 7 h after allergen was 25.5 and 8.8% respectively (mean difference 16.7%; 95% CI 4, 29%; p < 0.02). The methacholine PD20 fell significantly after allergen with placebo but not with PGE2. The difference was 1.5 doubling doses at both 4 and 7 h (p < 0.01 and p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)