Chemically stable analogs of peptide leukotrienes (LT) have been developed in our laboratories by replacement of the natural triene backbone with a C 7H 15 substituted aromatic moiety (1). These analogs are potent agonists of airway smooth muscle. Substitution in the peptide region resulted in U19052, an LT receptor antagonist. U19052 antagonized LT-induced contractions of guinea-pig tracheal spirals in a concentration-related manner. The pA 2 values versus LTD 4 and LTE 4 were 6.0 and 5.7, respectively, with slopes which were not significantly different from unity. LTC 4-induced contractions were antagonized by U19052 with a pK B of 5.6 obtained either in the absence of presence of L-serine borate. In contrast, carbachol and histamine concentration-response curves were not altered by U19052. LTD 4 or LTE 4 contractions of isolated guinea-pig ileum were antagonized by U19052 with pK B values of 7.2. The results indicate that potent selective LT antagonists can be developed from stable analogs of leukotrienes. U19052, an example of this series, appears to be as effective in antagonizing LTC 4- as well as LTD 4- and LTE 4-induced contractions in guinea-pig tracheal spirals.