OBJECTIVE: To evaluate the hypothesis that Arg16Gly polymorphism in the beta-2 adrenergic receptor (β2AR) is associated with the outcome to the antidepressant treatment. METHODS: A case-control study was performed among patients diagnosed with depression attending several outpatient clinics. They were evaluated and characterized for mood symptoms and response to the antidepressant treatment using the Semi-Structured Interview Guide of the Hamilton Depressive Scale (SIGH-D; 17 items) by a psychiatric specialist. Their genomic DNA was amplified by means of the polymerase chain reaction (PCR), and the polymorphism Arg16Gly of the β2AR gene was determined by restriction fragment length polymorphism (RFLP). Subsequently, the allelic frequencies of the polymorphisms were compared between two groups: 47 with suboptimal response (cases), and 37 with good response (controls). RESULTS: The frequency of the Arg16 allele was significantly higher when comparing cases and controls (52.1% and 33.3%, respectively. Chi(2)= 5.8, odds ratio=2.18, P= 0.016). CONCLUSION: An association was found between the response to antidepressant treatment and the Arg16Gly polymorphism of the β2AR. Further studies could help to establish the role of this polymorphism as a genetic factor predisposing to the drug response in depression.