In pediatric exercise testing, conventional measures of aerobic exercise function such as maximal O2 uptake or the ventilatory anaerobic threshold (VAT) use only one value for the assessment of exercise capacity. We studied a more comprehensive approach to evaluate aerobic exercise function by analyzing the steepness of the slope of CO2 production (VCO2) vs. VO2 above the VAT (S3). This was calculated in 32 patients operated on for congenital heart disease [16 for transposition of the great arteries (TGA) and 16 for tetralogy of Fallot (TF)] and was compared with 16 age-matched controls (nl). The results show that the reproducibility of this new assessment method was excellent (coefficient of variation for S3: 8.6%). S3 was significantly steeper (P<0.05) in the patients (1.31 +/- 0.22 for TGA and 1.28 +/- 0.16 for TF) compared with the nl (1.10 +/- 0.22). Also, the difference between S3 and the slope of VCO2 vs. VO2 below the VAT was significantly higher in the patients (0.37 +/- 0.22 for TGA and 0.31 +/- 0.10 for TF) than in controls (0.22 +/- 0.06). The steeper slopes were associated with lower than normal values for VAT and O2 during exercise. It is concluded that the analysis of the steepness of the slope of CO2 is a sensitive, reproducible, and objective approach to evaluate the integrative cardiopulmonary response to exercise. It complements the assessment of a subnormal VAT by reflecting the extent of anaerobic metabolism.