Although numerous psychotropic medications have a reported efficacy in posttraumatic stress disorder (PTSD), treatment of the condition remains largely empirical. The animal model of inescapable stress (IS) produces many physiological changes similar to PTSD in humans. The azapirones (e.g., buspirone, gepirone) are effective in alleviating the signs of IS in animals and should theoretically be effective in alleviating the symptoms of PTSD in humans. An open trial of buspirone in 8 patients meeting DSM-III-R criteria for posttraumatic stress disorder was conducted. Measurement tools included the Structured Interview for PTSD (SI-PTSD), Impact of Life Events Scale (ILES), and Beck Depression Inventory (BDI). Seven out of 8 patients exhibited a significant reduction in symptoms as measured by the SI-PTSD and BDI. The response was less significant on the ILES. Buspirone may be effective in alleviating the symptoms of PTSD. Further clinical trials to confirm this apparent efficacy appear warranted.