Stimulation of the midbrain during acute combined arterial hypoxia and hypercapnea produces serious cardiac dysrhythmias which are not evoked when stimulation is elicited either with normal arterial blood gas tensions or with isolated mild hypercapnea. The cardiac dysrhythmias are mediated by both enhanced sympathetic and parasympathetic efferent discharge. The results support the concept that increased autonomic activity in combination with acute arterial hypoxia and hypercapnea contribute significantly to the exhibition of serious cardiac rhythm disturbances. Acute hypoxia appears to be the major determinant of such dysrhythmias.