In order to evaluate the presumed involvement of altered noradrenergic receptor sensitivity in the switch process from depression into mania, we explored the relationship between pretreatment 3-methoxy-4-hydroxy-phenylglycol (MHPG) and tricyclic-induced mania or hypomania in bipolar depressed patients. Within the group of patients developing mania or hypomania on tricyclics, there was a strong positive correlation between pretreatment 24-hour urinary MHPG and the latency of onset of the episode. This finding is consistent with both the reported differences in MHPG excretion between unipolar and bipolar patients and the postulated noradrenergic involvement in the switch process.