One of the most important methodological problems of the foreign gas rebreathing technique is that outcome of the measurements depends on procedural variables such as rebreathing frequency (RF), rebreathing bag volume (V(reb)), lung volume at start of rebreathing and intervals between measurements. Therefore, in 10 healthy males we investigated the effects of changes in ventilation pattern on cardiac output (CO) estimated by an N(2)O-rebreathing technique. Reducing the rebreathing volume (V(reb)) from 1.5 to 1.0 l diminished CO by 0.5 +/- 0.2 l min(-1), whereas an increase in V(reb) from 1.5 to 2.5 l had no effects. CO was 1.0 +/- 0.2 l min(-1) higher when, rebreathing was performed after a forced expiration than following a normal tidal expiration. Serial determinations of CO required a 3-min interval between the measurements to avoid effects of recirculation of N(2)O. Changing RF from 15 to 30 breaths min(-1) or adding serial dead space by up to 600 ml did not affect the determination of CO. In conclusion, the rebreathing procedure for determination of CO at rest should be performed following a normal tidal expiration with a rebreathing bag volume of between 1.5 and 2.5 l and with manoeuvres separated by at least 3-5 min. Variations in RF within the physiological range from 15 to 30 breaths min(-1) do not affect outcome of the measurements.