The interaction of medullary and carotid chemoreceptors during mild stimulation was investigated in 44 experiments on 6 chloralose-urethane anesthetized mongrel dogs using a donor-perfused, bilateral carotid sinus preparation. The donor dog breathed hypoxic mixtures (average PaO2 of 78 mm Hg) and the experimental animal breathed hypercapnic mixtures (average PACO2 of 49 mm Hg) in order to separately or simultaneously stimulate both chemoreceptor areas at low levels. After 4 min, the changes of tidal volume (VT), respiratory rate (f) and minute ventilation (VI), as a percentage of the control value, were compared to test whether the sums of the changes for separate stimuli were the same as for simultaneous stimuli, i.e. additive chemoreceptor effects. The simultaneous stimuli had significantly (P less than 0.05) greater responses for VT (19% greater than 5%) and VI (42% greater than 13%), but not for f (23% = 9%). Stepwise multiple regression studies of the response/control ratios on the blood gas values showed that multiplicative interaction terms accounted for more of the variance than additive terms for VT, f and VI and yielded equations which had overall significant slopes. We conclude that this evidence demonstrates that the two chemoreceptor effects combine synergistically at low levels of stimulation.