Although the temperature-responsive neurons in the preoptic/anterior hypothalamic region, midbrain and the medulla oblongata show responsiveness to endogenous pyrogen (EP) injected systemically and locally, the question as to whether EP acts directly on these neurons per still remains unknown. To answer this question the experiments were attempted to administer EP, partially purified by ultrafiltration, onto the medullary temperature-responsive neurons in the rabbits, using method of micro-electrophoretical application. Before the application, it was proved that this partially purified EP could be transported through the tip of a five-barrelled electrode with micro-electrophoretical application. A total of 69 neurons was examined for the action of EP. Twenty-two out of 35 temperature-responsive neurons examined changed their activities in response to the EP applied with a positive current over 50 nA. None of the 23 temperature-insensitive neurons was affected by the application of the EP. All of these 58 nurons did not respond to heated EP or saline with the same current but excited to sodium glutamate. Ten of 69 nurons were affected by the sodium ion. From these results it is concluded that the EP acts very closely or directly onto the limited temperature-responsive neurons in the medulla.