Differences between the size and shape of spacers may affect the emitted dose and provide different effects when interchanged during routine use. Using a urinary pharmacokinetic method we have measured the relative lung and systemic bioavailability from urinary salbutamol excretion 30 min (USAL0.5) and 24 h (USAL24), respectively, after the inhalation of two 100-μg doses from a Ventolin Evohaler when used alone (MDI) and when attached to the Volumatic (VOL) or the Aerochamber Plus (AERO) spacers. The in-vitro properties of the emitted dose were determined. The mean (s.d.) USAL0.5 values following MDI, VOL and AERO (n = 13 volunteers) were 5.7 (1.9), 16.4 (8.2) and 14.8 (7.4) μg, respectively. VOL and AERO were significantly greater (P < 0.001 and < 0.01, respectively) than MDI. Comparison of VOL and AERO was similar with a mean ratio (90% confidence interval) of 108.2 (84.5, 138.6)%. USAL24 values between the three inhalation methods were similar. The values for the mean (s.d.) fine particle dose of two 100-μg doses emitted from MDI, VOL and AERO were 83.0 (6.8), 83.6 (4.6) and 73.6 (2.9) μg and the mass median aerodynamic diameters were 2.7 (0.03), 2.8 (0.07) and 2.9 (0.10) μm, respectively. The results showed that during routine use the Volumatic and the Aerochamber Plus spacers should provide similar lung and systemic delivery when attached to a Ventolin Evohaler.