Platelet monoamine oxidase (MAO) activity was studied in 33 in-patients with bipolar and schizoaffective disorder who were treated with lithium. Platelet MAO activity was found to increase following 10–41 days of lithium treatment compared to a prior drug free period, and the increase was positively correlated with the duration of lithium treatment. The increase in platelet MAO activity was not correlated with clinical improvement as measured by the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment Scale (GAS). The number of platelets per unit of blood was also significantly correlated with the number of days of lithium treatment. However, the increase in the number of platelets in lithium-treated patients was not correlated with the increase in MAO activity and thus appears not to account for it. These results indicate that studies relating platelet MAO activity to psychiatric diagnosis should be interpreted cautiously if patients are receiving lithium carbonate.