The growth hormone (GH) response to clonidine was evaluated in 28 acutely depressed male patients, 17 remitted depressed patients, and 26 normal control subjects. The GH response to clonidine was blunted (delta less than 4 ng/ml) in a significantly increased proportion of both acute and remitted patients compared to control subjects. Covarying for age effects, the GH response to clonidine (as area-under-the-curve) was not significantly different between any of the three groups, but was significantly diminished in both the acute and remitted depressed patients who were ever hospitalized for an episode of depression, compared to control subjects. Six patients studied in both the acute and remitted states were blunted in both states. These findings could not be accounted for by other clinical and demographic variables including weight, time off antidepressants, severity of current depressive symptoms, and subtype of depression. These results raise the possibility that the blunted GH response to clonidine may represent a state-independent correlate of some forms of severe depression. Issues regarding the specificity and interpretation of this finding require further clarification.