Poor inhalation technique is prevalent in asthmatics using standard metered dose inhalers (MDI). Both dry powder inhalers (DPI) and breath activated MDIs offer a solution to this problem. Our aim was to compare the lung delivery of salbutamol from two DPIs, Diskhaler and Diskus (Accuhaler), and the Easi-Breathe breath activated MDI. Ten healthy volunteers mean (SEM) age 24.0 years (1.7) were studied in a randomized single (investigator) blind crossover design. Single 1200 micrograms nominal doses of salbutamol via Diskhaler and Diskus (6 sequential 200 micrograms puffs) and Easi-Breathe (12 sequential 100 micrograms puffs) were given over 6 min. Mouth rinsing was performed after every inhalation sequence. Lung delivery was evaluated by measuring the early lung absorption profile of salbutamol at 5, 10, 15 and 20 min after inhalation, with calculation of peak (Cmax) and average over 20 min (Cav) concentration (ng/ml). Both the Diskhaler and the Easi-Breathe produced significantly greater salbutamol Cmax and Cav than Diskus (as mean and 96% CI for difference vs. Diskus): [Cmax] Diskus 3.22 vs. Diskhaler 4.35 (95% CI 0.19 to 2.08), vs. Easi-Breathe 3.98 (95% CI -0.18 to 1.71). [Cav] Diskus 2.62 vs. Diskhaler 3.95 (95% CI 0.52 to 2.14), vs. Easi-Breathe 3.52 (95% CI 0.09 to 1.71). For Cav this amounted to a 1.51-fold difference (95% CI 1.35 to 1.68) between Diskhaler vs. Diskus, and a 1.36-fold difference (95% CI 1.03 to 1.69) for Easi-Breathe vs. Diskus. In conclusion we found that, in vivo, the Diskus DPI produced significantly lower lung delivery for the same nominal dose of salbutamol than either Diskhaler DPI or the Easi-Breathe pressurised aerosol. This shows that breath activated inhaler devices may have different in vivo deposition characteristics for delivering the same drug.