We have developed a model-based approach for estimating the dynamic effects of respiration on heart rate ("RSA") and arterial pressure ("MER"), along with the baroreflex response ("ABR") and the feedforward effect of heart rate on blood pressure ("CID") from a single test procedure. Respiration, heart rate, continuous blood pressure and other polysomnographic variables were monitored in 9 normals and 8 untreated patients with obstructive sleep apnea (OSA). A computer-controlled ventilator was used to vary ventilatory pattern in a randomized breath-to-breath sequence. Using closed-loop model analysis, we estimated the parameters that characterize RSA, ABR, CID and MER. RSA and ABR gains were significantly lower in OSA than normals. During sleep, ABR gain increased threefold in normals but remained unchanged in OSA. CID gain was higher in OSA relative to normals, suggesting increased peripheral vascular resistance. MER gain was also higher in OSA, but only in wakefulness. Apart from increased mean heart rate in OSA, there were no significant differences in other summary and spectral measures of cardiovascular variability. Our approach represents a sensitive, clinically practicable and comprehensive means of assessing autonomic function in OSA during both wakefulness and sleep.