The cerebral ventricular system of anesthetized dogs was perfused with synthetic isotonic CSF and, for 80 s intervals, with hypertonic CSF of various compositions. Hypertonic perfusion evoked centrally mediated marked increases in arterial blood pressure, heart rate, respiratory rate, and ventilation and, after some delay, an excitatory reaction resembling arousal. The responses were coordinated in time with the induced CSF hypertonicity, graded in relation to its magnitude, and reversible on return to isotonicity. The effects, which seemed to be elicited from periventricular structures in the brain stem, were more pronounced and consistent when CSF hypertonicity was produced by adding NaCl or Na-lactate than monosacharides to the isotonic CSF solution. Analysis of the cardiobascular responses indicated that they were caused by increased sympathetic vasoconstrictor and cardiac accelerance fibre activity and by inhibition of vagal discharge to the heart. The described pattern of response much resembles that evoked by physical exercise, a state which might lead to osmolar changes in the brain and CSF of a similar kind to that in the present study as a consequence of the pronounced work-induced arterial hyperosmolality. It is suggested that such an osmotic mechanism might constitute a "metabolic link" in the centrally mediated circulatory and respiratory adjustments in exercise.