1. The rise (‘boost’) in carboxyhaemoglobin (HbCO) on smoking has been studied with alveolar carbon monoxide measurements before and after smoking a cigarette. We re-examined this in 28 subjects with HbCO values compared with rebreathing carbon monoxide [FAco(Rb)] and breath-hold alveolar carbon monoxide and oxygen concentrations, obtained after a 20 s breath-hold [FAco(Bh)] and FAo2(Bh), respectively]. Tests were done in the order FAco(Bh) and FAo2(Bh), FAco(Rb), FAco(Bh) and FAo2(Bh) before and after smoking a single cigarette, with HbCO being measured 1 min before and after smoking. 2. The changes were expressed as the relative boost: For HbCO the average value was 23.7%, but the FAco(Rb) boost was only 9.8%. The first post-smoking FAco(Bh) boost was 3.9% (5.0 min after smoking), rising to 8.5% 9.4 min later. 3. The FAo2(Bh) values fell from a mean of 15.4% before smoking to 14.3% (5.0 min after smoking) then recovered to 15.4% 9.4 min later, suggesting a transient effect on pulmonary gas exchange. Correction of the first post-smoke FAco(Bh) data for this effect increased the relative boost to 11.5%. Routine FAo2(Bh) measurements may be useful in further smoking studies. 4. We conclude that none of the alveolar sampling techniques gives a reliable measurement of the acute HbCO changes associated with smoking.