Plasma noradrenaline (NA), adrenaline (A), corticosterone (CS) and glucose concentrations were determined in blood frequently sampled via a cardiac catheter from freely behaving rats exposed to five successive trials of water-immersion stress (WIS) with an interval between successive trials (interstressor interval; ISI) of either 24 hr or 72 hr. The first, acute exposure to WIS was accompanied by increased levels of plasma NA, A, CS and glucose which were substantially higher than those associated with handling or placement into a new cage. The magnitudes of the WIS-induced plasma NA, A, CS and glucose responses gradually declined across trials. However, five WIS exposures at a 24-hr ISI resulted in a faster and greater decrement of the plasma A, CS and glucose responses than five exposures at a 72-hr ISI. The data indicate that frequency of stressor presentation (i.e., length of interstressor interval) affects the adaptation pattern of neuroendocrine and metabolic responses to chronic intermittent stress. This finding supports the hypothesis that neuroendocrine adaptation to stress is (at least partly) similar to the process of behavioral or neurophysiological habituation to a sensory stimulus.