The aims of this study were (a) to apply in the animal with intact baroreflex a two-point method for estimation of overall, effective open-loop gain, G0e, which results from the combined action of baroregulation and total systemic autoregulation on peripheral resistance; (b) to predict specific baroreflex gain by correcting the effective gain for the autoregulation gain; and (c) to discuss why the effective gain is usually as low as 1–2 units. G0e was estimated from two measurements of both cardiac output, Q, and mean systemic arterial pressure, P: one in the reference state (set-point) and the other in a steady-state reached 1–3 min after a small cardiac output perturbation. In anaesthetized cats and dogs a cardiac output perturbation was accomplished by partial occlusion of the inferior vena cava and by cardiac pacing, respectively. Average (±S.E.M.) estimates of G0e were 1.4 ± 0.2 (n = 8) in the cat and 1.5 ± 0.4 (n = 5) in the dog. The specific baroreflex open-loop gain, G0b, found after correction for total systemic autoregulation, was 3.3 ± 0.4 in the cat and 2.8 ± 0.8 in the dog. A model-based analysis showed that, with G0e as low as 1.4, the closed-loop response of P to a stepwise perturbation in Q results in damped oscillations that disappear in about 1 min. The amplitude and duration of these oscillations, which have a frequency of about 0.1 Hz, increase with increasing G0e and cause instability when G0e is about 3. We conclude that autoregulation reduces the effectiveness of baroreflex gain by about 55%, thereby preventing instability of blood pressure response.