BACKGROUND This study was designed to evaluate the anxiolytic efficacy of buspirone in patients with a diagnosis of generalized anxiety disorder (GAD) with coexisting mild depressive symptoms. METHODS Patients who participated in this multicenter study scored >/= 18 on the Hamilton Rating Scale for Anxiety (HAM-A) and between 12 and 17 on the Hamilton Rating Scale for Depression (HAM-D). Following a 7- to 10-day placebo lead-in phase, patients who continued to qualify were randomly assigned to receive either buspirone titrated from 15 to 45 mg/day (N = 80) or placebo (N = 82) for the next 6 weeks. 121 patients completed 6 weeks of treatment. The primary efficacy measure was the HAM-A, taken weekly during the study. RESULTS Buspirone-treated patients averaged a 12.4-point reduction from their baseline total HAM-A score of 24.9, while their counterparts on placebo averaged a 9.5-point reduction from their mean baseline total HAM-A score of 25.6. This 2.9-point difference in HAM-A reductions between treatment groups was significantly different (p < .03). Buspirone patients decreased their HAM-D scores by an average 5.7 points from their mean baseline total HAM-D score of 15.8, while placebo patients decreased their HAM-D scores by an average 3.5 points from their mean baseline score of 16.3 (p < .05). Overall, the incidence of adverse events was similar for both treatment groups, but buspirone-treated patients reported significantly more nausea, dizziness, somnolence, and sweating than placebo patients. CONCLUSIONS Buspirone is superior to placebo in improving anxiety and depressive symptoms in GAD patients who have coexisting depressive symptoms.