Salmeterol is a new beta 2-selective agonist with a long duration of action. We compared the effect of 50 micrograms salmeterol administered by metered dose inhaler (MDI) and dry powder inhaler (DPI), with 200 micrograms albuterol (by MDI) on FEV1 and histamine-induced bronchoconstriction in 12 asthmatic subjects in a double-blind, placebo-controlled crossover study. Subjects were studied for 12 h on four occasions with a histamine challenge test at 1, 4, 8, and 12 h, the response being measured as the dose of histamine causing a 20% fall in FEV1 (PD20). There was no difference in the mean +/- standard error of the mean maximum increase in FEV1 between salmeterol MDI, salmeterol DPI, or albuterol (0.57 +/- 0.078, 0.54 +/- 0.089, and 0.49 +/- 0.081 L, respectively); the increase following placebo was 0.25 +/- 0.082 L. The area under the 12-h time-response curve for FEV1 was greater for both formulations of salmeterol (MDI and DPI) than for albuterol. The three active drugs protected against histamine-induced bronchoconstriction. The increase in PD20 at 1 and 12 h and the area under the 12-h time-response curve for PD20 were greater following both formulations of salmeterol than after albuterol. The greater change in geometric mean PD20 values at 1 h after both formulations of salmeterol (2.21 and 1.88 mumol) relative to albuterol (0.98 mumol) suggests that despite similar effects on FEV1 the doses used do not have an equivalent effect on the airways.(ABSTRACT TRUNCATED AT 250 WORDS)