Intravenous injection of dopamine (DA) has consistently been shown to depress minute ventilation (E). Whereas at low dosage (10 µg/kg) this effect may be accounted for by inhibition of the carotid sinus nerve chemosensory discharge (CSNCD), other mechanisms appear to be involved with large dosage (50 µg/kg). The purpose of this study was to elucidate the mechanisms of DA-induced E depression. The effects of intravenous injection of DA doses ranging from 1 to 200 µg/kg were studied in 18 anesthetized cats. DA was injected during air and O₂ breathing, after -adrenergic blockade by phenoxybenzamine and after baro- and chemodenervation. E and CSNCD were also simultaneously recorded on four occasions. In contrast to that with use of low-dose DA, E depression induced by high-dose DA was dissociated from CSNCD, persisted during 100% O₂ breathing, and was significantly correlated with the rise in arterial blood pressure. Although blunted, E depression was still present after complete chemo- and barodenervation but was suppressed by blocking of the concomitant vasoconstriction with phenoxybenzamine. It is concluded that reflexes of circulatory origin contribute to the E depression induced by large-dose DA, in addition to its effects on arterial chemoreceptors. The contribution of baroreceptor stimulation and peripheral vasoconstriction is discussed.