In patients with chronic heart failure (CHF), the anaerobic threshold by gas exchange (ATge) represents a potentially useful parameter for assessing functional disability and the response to therapeutic interventions designed to improve exercise tolerance. We measured the ventilatory, hemodynamic, and metabolic responses to maximal bicycle exercise in 64 patients with CHF and 38 age-matched normal subjects. The ratio of ventilation to carbon dioxide production (VE/VCO2) was increased during exercise in patients as compared with normal subjects although VE was closely related to VCO2 in both individual normal subjects and patients (all, r greater than 0.92, p less than 0.01). Increased VE/VCO2 in patients was unrelated to increased pulmonary vascular pressures but was closely linked to increases in the pulmonary dead space to tidal volume ratio (Vd/Vt). Despite hemodynamic abnormalities in patients, PaCO2 was regulated at normal levels during exercise. In a second study, we determined the ATge in 18 patients with CHF and 18 normal subjects by the ventilatory equivalents method. The ATge could be identified from unaveraged breath-by-breath data as the initial increase in VE/VO2 without an increase in the VE/VCO2 in 15 of 18 patients and in 16 of 18 normal subjects. The ATge demonstrated good day-to-day reproducibility (r = 0.91, p less than 0.001, SEE = 1.74 ml/kg/min) and low interobserver variability and was associated with comparable increases in arterial lactate in the two groups above the resting value, 0.9 +/- 0.4 mM/l in patients and 0.8 +/- 0.5 mM/l in normal subjects. To examine the effects of a chronic intervention on the ATge, 12 patients with CHF underwent exercise training for 4-6 months. Training resulted in a 23% improvement in peak VO2 and a decrease in blood lactate accumulation during submaximal exercise. This was associated with decreased VE and VCO2 during submaximal exercise, an increased VO2 at which the ATge occurred from 10.1 +/- 1.2 ml/kg/min to 12.1 +/- 2.6 ml/kg/min (p less than 0.01) and an increase in exercise duration during a symptom-limited, constant work-rate protocol (938 +/- 110 seconds vs. 1,421 +/- 691 seconds, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)