The authors compared the antimanic effects of a verapamil-magnesium oxide (V-M) combination with a verapamil-placebo combination (V-P) in patients pretreated with verapamil. BPRS scores and serum magnesium levels were compared. The V-M combination was found to be significantly more effective than V-P in reducing manic symptoms (P=0.015). Serum magnesium levels were significantly higher in the V-M group (P<0.04). These data suggest that magnesium may increase antimanic efficacy of verapamil by mechanisms which may operate at the intracellular level. The magnesium-verapamil combination may have clinical application as an adjunct to verapamil in the maintenance therapy of mania.