We measured the growth hormone (GH) response to clonidine (an alpha-2-adrenergic agonist) and to apomorphine (a dopaminergic agonist) in 15 major endogenous and 15 minor depressive in-patients matched for gender and age. Results showed a significantly smaller GH response in the major depressives to both Clonidine (P<0.01) and apomorphine (P<0.001). No significant difference existed between the two groups with regard to changes in blood pressure and pulse rate during either test. While major depressives showed a trend toward smaller sedative side-effects than minor depressives after Clonidine, they showed significantly smaller sedative and gastro-intestinal side-effects after apomorphine. No significant correlation was present either in the major depressive or in the minor depressive group between the GH responses following Clonidine and apomorphine challenges. These results support the hypothesis of both noradrenergic and dopaminergic neurotransmitter disturbances in major depression, with individual variability with regard to those biochemical anomalies.