There is controversy as to whether effects on mood play a role in mediating the response to corticosteroids in chronic obstructive pulmonary disease (COPD). If alterations in mood are important, it is conceivable that psychotropic drugs such as mianserin might produce similar responses to prednisolone in patients with COPD. Twelve patients age 62.5 y, with FEV1 29% of predicted and < 15% reversibility to salbutamol completed a randomised, double-blind crossover study. After an initial three week placebo run-in period patients received three weeks of prednisolone 40 mg daily or mianserin 60-90 mg daily with an intervening three week placebo washout period. Full respiratory function tests, bicycle ergometry and 6 minute walks were performed before and after the run-in and at the end of each period. Psychological and functional assessments were also made at each visit. Prednisolone significantly increased FVC, maximum ventilation (VEmax) and maximum heart rate (HRmax) compared with placebo, with mean for the difference of 0.25 l, 2.56 l.min-1 and 12 beats.min-1 respectively. FVC, maximum oxygen uptake (VO2max) and HRmax were also significantly increased with prednisolone compared with mianserin. Anxiety scores were significantly lower with prednisolone compared with placebo. In contrast, mianserin had no significant effects on lung function, exercise or psychological parameters compared with placebo. The improvements in ventilation, exercise and anxiety scores following treatment with prednisolone were not reproduced by mianserin, suggesting that the effects of prednisolone in COPD are unlikely to be due to alterations in mood.