To evaluate seasonal influences on the dexamethasone suppression test (DST), cortisol and melatonin responses to dexamethasone were assessed in drug-treated chronic schizophrenics and in drug-free healthy volunteers in different seasons of the year, according to a longitudinal study design. In schizophrenic patients, there was a greater rate of cortisol non-suppression to DST in February as compared to November and May (χ² = 4.5, p = 0.03) with no significant differences in pre- and post-dexamethasone plasma cortisol levels. In healthy volunteers, in contrast, no seasonal variation in DST results was observed. Moreover, dexamethasone administration did not significantly affect morning plasma melatonin levels in either patients or healthy controls. These findings suggest that seasonality may be of critical importance in evaluating DST results in schizophrenic patients, but not in healthy subjects.