Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV, 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of > 20% in FEV, (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0-06, 0-12, 025, 0-5, 1-0, 2-0, and 4-0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV, being recorded after inhalation ofeach concentration. Dose dependent falls in FEV, occurred in five non-smokers (geometric mean 1 76, 95% confidence limits 0-87-3-53 mg/ml) and three smokers (0-23, 0O07-0 78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 ,ug of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.Bacteria elaborate chemotactic factors for leucocytes.'-3 These factors have been isolated and characterised as small molecular weight peptides."5 In subsequent studies of the structure-activity relations of synthetic chemotactic peptides6 the acylated tripeptide formyl-methionyl-leucyl-phenylalanine (FMLP) was shown to be the most active chemotactic agent.With an ED_, for rabbit neutrophil chemotaxis of 70 pmol/l, FMLP is one of the most potent chemotaxins known. The well defined chemical structure of the ligand has permitted detailed studies of the nature of the receptor that is present on macrophages and