To study the dose-response relationship of salmeterol for protection against a naturally occurring stimulus, isocapnic hyperventilation tests of cold air were done in 16 asthmatic patients. The subjects inhaled either 50 micrograms salmeterol, salbutamol 200 micrograms, or placebo in a double-blind, randomised, cross-over study. The FEV1 was measured prior to medication and the provocative ventilation (PV20) required to induce a 20% fall in FEV1 was calculated by linear interpolation from ventilation-response curves obtained 0.5, 4, 8, and 12 h after medication. Following salbutamol, the mean FEV1 were 4.11, 3.89, 3.58, and 3.55 l, with a significant difference from placebo up to 4 h. Following salmeterol, mean FEV1 values were 3.95, 4.10, 3.93, and 3.88 l, with a significant difference from placebo up to 12 h. The mean PV20FEV1 after salbutamol was 78.8, 58.5, 52.7, and 48.4 l.min-1, the 0.5 h value being significantly different from placebo. After salmeterol, the mean PV20FEV1 values were 84.6, 82.5, 67.8, and 65.8 l.min-1, with a significant difference from placebo up to 12 h. We conclude that, besides its long-lasting bronchodilating effect, salmeterol protects against hyperventilation-induced bronchoconstriction for at least 12 h.