BACKGROUND Heartbeat-related pressure oscillations appear at the airway opening. We investigated whether these cardiogenic oscillations (COS) - extracted from spontaneous breathing signals - reflect the compliance of the respiratory system. METHODS Fifteen volunteers breathed spontaneously at normal or reduced chest wall compliance, i.e. with and without thorax strapping, and at normal or reduced lung compliance, induced by positive end-expiratory pressure (PEEP). COS-related signals were extracted by averaging the flow and pressure curve sections, temporally aligned to the electrocardiogram signal. RESULTS COS-related airway pressure and flow curves correlated closely for each subject (r(2) =0.97 ± 0.02, P<0.0001). At the unstrapped thorax, the oscillation's amplitudes were 0.07 ± 0.03 cm H(2) O (pressure) and 22 ± 10 ml/s (flow). COS-related pressure amplitudes correlated closely with the ratio of tidal volume divided by pressure amplitude (r(2) =0.88, P<0.001) and furthermore increased with either thorax strapping (P<0.001) or with increasing PEEP (P=0.049). CONCLUSIONS We conclude that COS extracted from the pressure and flow signal reflect the compliance of the respiratory system and could potentially allow estimating respiratory system mechanics during spontaneous breathing.