The purpose of this study was to assess the prevalence of distress, anxiety, and depression in persons with human immunodeficiency virus (HIV) infection and determine the feasibility of screening in an urban HIV primary care setting. A convenience sample of 101 patients in the waiting room of an acquired immunodeficiency syndrome clinic completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer. The patient's demographic, medical, and psychiatric histories were obtained through chart review. The results of the Distress Thermometer revealed that 72.3% had a score of 5 or greater, demonstrating high distress. The results of the HADS revealed that 70.3% had high anxiety, with a score of 7 or greater. On the HADS depression questions, 45.5% had a score of 7 or greater, indicating depression. Analysis of the total HADS scores, including anxiety and depression, revealed that 53.5% had a score of greater than 15 and were experiencing significant distress. Patients with high viral loads were more likely to be distressed (P < 0.0005). Patients with high viral loads were also more likely to have higher anxiety or depression scores on the HADS. Patients who had CD4 counts higher than 500/mm3 were less likely to be depressed. This study demonstrates a high prevalence of distress, anxiety, and depression among persons with HIV. The HADS and the Distress Thermometer showed a good correlation with each other (P < 0.0005), and these questionnaires can provide a simple and efficient method for rapid screening in an HIV clinic setting.