As histamine and methacholine are metabolised within minutes, one would not expect that the dose-response curves upon challenge with these agonists is affected by cumulatative effects. After a single dose of histamine or methacholine the peak action on airway calibre occurred in a similar interval (1-4 min). However, the mean duration of the subsequent plateau was 16.8 (SD 9.8) min for histamine, and 74.6 (SD 53.7) min for methacholine, respectively. In addition, the recovery phase from the end of the plateau to base line lasted 25.5 (SD 14.4) min for histamine and 56.7 (SD 38.3) min for methacholine, respectively [1]. Hence, a short half-life of the pharmacological substances does not necessarily mean that the biological effects on the airways are equally shortlived. In individual subjects an effect of inhaled histamine on airway diameter in usual dosages may be detectable for up to 70 minutes [2-4]. Therefore, when subsequent doses are inhaled a small cumulative effect is to be expected.