Despite the availability of atypical antipsychotics, the treatment of negative symptoms in schizophrenia remains a challenge. This study was designed to confirm the positive effect observed in our pilot study with paroxetine as augmentation to antipsychotics in the treatment of negative symptoms in chronic schizophrenia. Twenty-nine patients with chronic schizophrenia, as defined by DSM-IV, who scored at least 20 points on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) were randomized for treatment with 30 mg paroxetine or placebo in a double-blind, placebo-controlled study for 12 weeks. Ratings included the PANSS, the Hamilton Rating Scale for Depression (HAM-D) and scales for extrapyramidal side-effects. An intention-to-treat analysis was based on the 25 patients who were available for at least one follow-up assessment. The last observation carried forward principle was applied. The mean score of the negative subscale of the PANSS decreased in both groups. Using an analysis of covariance, there was a significant treatment effect with paroxetine compared to placebo with respect to negative symptoms (-4.53; 95% confidence interval -9.054 to -0.015). The mean HAM-D scores remained almost constant. The study suggests the efficacy of paroxetine with respect to the treatment of negative symptoms in chronic schizophrenia.