We have previously shown that excitation of certain neurons in the ventromedial nucleus of the hypothalamus (VMH) of rats induces hyperrunning activity. The present study investigated the involvement of these VMH neurons in inducing excessive running under the activity-stress paradigm. The VMH of 6-week-old male rats was bilaterally lesioned by administration of kainic acid. Control animals received saline in the VMH. They were housed in running-wheel activity cages with free access to food for 6 days of the recovering period, and then fed 1 h each day for 6 days. Control animals exhibited marked increases in both running activity and its light/dark ratio, and developed stomach ulcers. In contrast, animals with bilateral VMH lesions showed a significantly attenuated increase in running activity and no change in light/dark ratio. VMH lesions also suppressed stomach ulceration. These results suggest that VMH neurons play a crucial role in inducing excessive running and stomach ulceration during exposure to the activity-stress paradigm.