A large number of studies suggest that dopaminergic function may be impaired in depressed patients, particularly in bipolar patients. The dopamine D2/D1 agonist apomorphine (APO) can be useful in the evaluation of dopaminergic function. However, most studies show conflicting results in APO test responses when evaluating unipolar and bipolar depressed patients. Thus, the objective of this study was to apply the APO test to assess whether hypothalamic-pituitary dopaminergic function is altered in unipolar and bipolar depression. We evaluated multihormonal responses to APO test (0.75 mg subcutaneous) in 134 drug-free DSM-IV major depressed inpatients (54 with bipolar depression [BD] and 80 with unipolar depression [UD]), compared with 36 healthy controls (HCs). We also examined the cortisol response to the dexamethasone suppression test (DST, 1 mg orally) in all subjects. No significant differences in prolactin (PRL), cortisol, adrenocorticotropin (ACTH) or growth hormone (GH) baseline values were found across the three groups. ACTH/cortisol and GH responses to APO were also comparable. BD patients showed lower PRL suppression to APO than did UD patients and HCs (both p < 0.00001). Although responses to DST were comparable between UD and BD patients, the former exhibited higher post-DST cortisol levels than did HCs (p < 0.05). Our results suggest that BD patients, unlike UD patients, have altered post-synaptic D2 receptor sensitivity at the pituitary level. This alteration does not seem secondary to hypercortisolemia. These findings, if confirmed by other studies with larger samples, may support the use of dopamine agents in BD patients treatment.