1 Fourteen asthmatics (mean ± s.e. mean baseline FEV1 62 ± 6% of predicted) were given cumulative doubling doses of salbutamol by metered-dose inhaler as follows: 100 ,ug, 200 pg, 500 pg, 1000 pug, 2000 ,ug, 4000 ,ug. 2 Airways, tremor, haemodynamic and cyclic AMP responses were measured at each dose increment (made every 20 min). 3 There was a linear log dose-response relationship for each airways parameter (FEV1, VC, sGaw, FEF 50%). The plateau in the dose-response curve was not reached within our dose range. These changes were also mirrored in cyclic AMP responses. 4 There was a wide range in maximum airways response expressed in terms of absolute increase over baseline (95% confidence intervals: AFEV1 667-1483 ml; A VC 689-1695 ml; A sGaw 0.92-4.50 s-1 kPa-1; A FEF 50% 0.94-2.15 1 s-). Patients with a lower baseline showed a greater response in terms of percent increase in FEV1 (r = -0.83, P < 0.001). There was however, no correlation between baseline airway calibre and the dose required for maximum bronchodilatation.5 There were objective increases (mean ± s.e. mean) in both heart rate (maximum A HR of 14 ± 5 beats min-' at 4000 ,ug) and tremor power (maximum A Tr of 115 ± 44% at 2000 ,ug). These were not dose limiting side-effects as subjective symptoms were infrequent at higher doses. 6 Higher than conventional doses of salbutamol given by metered-dose inhaler may produce a distinct improvement in airways response without significant side-effects. There is a wide individual variation in airways response to inhaled salbutamol, although most patients required higher doses to achieve maximal bronchodilatation. The severity of asthma does not however predict the dose required for maximum airways response.