A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide antibiotic, clarithromycin, on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma. Adult asthma patients undergoing treatment with budesonide 400 microg b.i.d. and salbutamol 200 microg p.r.n. less than twice weekly were studied. Arm A (16 males/six females, aged 48 +/- 16 yrs) received clarithromycin 250 mg b.i.d. for 8 weeks, arm B (eight males/12 females, aged 42 +/- 12 yrs) clarithromycin 250 mg t.id. and arm C (six males/15 females, aged 41 +/- 16 yrs) placebo dextrose tablets. Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20). Median (interquartile range) PD20 in the three groups before and after treatment with clarithromycin were: arm A: 0.3 (0.1-1) and 1.3 (0.6-2) mg; arm B: 0.4 (0.1-0.9) and 2 (2-2) mg; and arm C: 0.4 (0.1-0.9) and 0.3 (0.1-0.6) mg, respectively. Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients. It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma.