Calcium (Ca) and magnesium (Mg) are involved in many processes related to depression. Evaluations of serum and plasma Ca and Mg levels in depressive disorders do not show consistent results. The few studies that examined their cerebrospinal fluid (CSF) levels tended to find no differences between depressed patients and controls. Because both hypercalcemia and hypomagnesemia are associated with depression, and as Mg may function as a Ca antagonist, it is suggested that the relationship between these cations could be different in depressed patients and controls. We examined CSF and serum Ca and Mg in acutely depressed patients diagnosed as having major depressive disorder or being in a depressive episode of bipolar disorder. Controls were subjects undergoing lumbar puncture as part of an evaluation for headache or suspected meningitis and found to demonstrate no physical or mental disorder. Serum and CSF Ca/Mg ratios were found to be elevated in the depressed patients compared with the controls. A retrospective analysis of previous trials assessing serum/plasma or CSF Ca and Mg does not seem to refute the findings of this study. We further discuss our findings in their relation to the acuteness of the depressive disorders.