In a multicenter, randomized, double-blind study, we compared the effects of nebulized (5 mg x 2) and intravenous (0.5 mg) albuterol (salbutamol) over 1 h in 47 patients admitted to hospital with severe acute asthma defined as a peak expiratory flow (PEF) below 150 L/min and hypercapnia (Pa(CO2) > or = 40 mm Hg). Additional treatment included nasal oxygen and hydrocortisone succinate. The efficacy was assessed after 1 h. In the group treated by nebulization (NEB group, n = 22) 19 (86%) patients (95% confidence interval: 65 to 97%) had been treated successfully according to predefined criteria, versus 12 (48%) patients (95% confidence interval: 28 to 69%) in the intravenously treated group (i.v. group, n = 25), p = 0.006. The mean increase in PEF was greater in the NEB group than in the i.v. group (+107 +/- 94 L/min versus +42 +/- 66 L/min, p = 0.01) as well as the decrease in Pa(CO2) values (-10 +/- 5 mm Hg versus -2 +/- 12 mm Hg, p < 0.01). Beta agonist-induced hypokalemia was more pronounced in the i.v. group than in the NEB group. We conclude that, in hypercapnic acute asthma, the nebulized route has a greater efficacy and fewer side effects than the intravenous route.