Eleven patients with severe COPD were examined to determine whether tolerance to beta 2-agonists developed after long-term inhalation therapy with these agents. Before the study all patients were on regular treatment with inhaled salbutamol for six months. At the beginning of the study, response of FEV1 to inhaled salbutamol was measured. Dose-response curves were measured after three weeks of treatment with ipratropium bromide and again after a three-week course of inhaled salbutamol. After ipratropium bromide treatment, responses to low doses of salbutamol tended to be larger than after salbutamol treatment, but differences were not significant. Three hours after the last inhalation of salbutamol the FEV1 was lower on days 1 and 42 than on day 21. We conclude that long-term inhalation therapy with beta 2-agonists in patients with COPD decreases the duration of the bronchodilation produced by the same agents but does not affect the peak response.