High concentrations of ambient anions (O2-) were used to augment treatment for 20 acutely manic male patients. Anions were produced by an anion generator in a sealed room. A double-blind crossover design was used, and responses were evaluated with the Brief Psychiatric Rating Scale by 2 blinded raters. This produced a significant antimanic effect: total rating scores declined with anion treatment. Presham and postsham total scores for these 5 were 31.3 and 31.6, respectively. Pretreatment and posttreatment total scores were 31.6 and 26.3, respectively. Previous research indicates a role for serotonin in producing this antimanic effect.