A woman with a recurrent episode of a depression that hitherto had been unipolar developed a hypomania the day after her treatment with paroxetine 20 mg/day was switched to venlafaxine 75 mg/day. The hypomanic symptoms subsided gradually as the dosage was reduced and the patient thereafter remained in a euthymic state while on venlafaxine at a dose of 18.75 mg/day. Three possible explanations are discussed for the patient's response: there was a pharmacokinetic interaction between paroxetine and venlafaxine, the patient had an idiosyncratic reaction to venlafaxine or venlafaxine inhibited the re-uptake of norepinephrin.