The effects of age and sex on the single-breath transfer factor (TLCO) estimated during exercise have been investigated in 80 normal subjects (40 men) divided equally into four groups: 1) 20-29 yrs; 2) 30-39 yrs; 3) 40-49 yrs and 4) 50-59 yrs. Oxygen consumption (VO2), cardiac frequency (fc), TLCO and transfer coefficient (KCO) were estimated at rest and at 25 W increments up to 100 W in women and 150 W in men. Quadratic regression equations were obtained for the relationships of TLCO and KCO to VO2, fc and workload (WL). TLCO and KCO at any WL, VO2 or fc were greatest in group 1 and least in group 4. The rate of decline of TLCO and KCO in men and women at l.min-1 VO2 was 0.063 and 0.031 mmol.min-1.kPa-1.yr-1 and 0.006 and 0.007 mmol.min-1.kPa-1.l-1.yr-1, respectively. Within each sex the curvilinearity of the relationships was similar regardless of age. At any WL, TLCO was greater in men than in women, whilst KCO was greater in women than in men. Sex differences were not abolished by correcting TLCO and KCO for anthropometric indices. We conclude that age and sex have significant effects on TLCO and KCO on exercise.