Since the patent on albuterol metered-dose inhalers (MDI) expired in 1989, several manufacturers have developed generic products. In order to determine whether one generic albuterol MDI is equivalent to a reference product (Ventolin MDI), we compared the relative efficacy of two puffs (180 micrograms) of each inhaler in 17 intermittent or mild chronic adult asthmatics (FEV1 48% to 77% predicted) in a randomized, single-blind, crossover manner. The test dose was the first two puffs out of each canister. Pulmonary function was measured before each test dose and at frequent intervals over eight hours. Baseline FEV1 values on both study days were within 20%. The mean +/- SD peak effect was 80.5 +/- 15.5% of maximum achievable improvement in FEV1 after the generic compared with 92.2 +/- 8.8% after Ventolin (P = .006). The area under the curve (AUC) for this same measurement during the first four hours was 242 +/- 75%.hr-1 after the generic compared with 297 +/- 40%.hr-1 after Ventolin, a mean difference of 19% (P = .002). The study was then repeated with the MDI primed prior to the test dose (ie, two puffs were first discharged into a waste basket) in subjects willing to return for re-study (n = 11). There was no significant difference in AUC in the second study: 215 +/- 77%.hr-1 after generic and 228 +/- 82%.hr-1 after Ventolin (P = .65); however, there was only a 35% chance of detecting a 20% difference in AUC with this sample size. These data indicate that, without priming, an MDI may deliver less drug, and thereby less therapeutic effect.(ABSTRACT TRUNCATED AT 250 WORDS)