Although distressing pain and other symptoms have been reported at all stages of HIV disease, studies have not taken account of the relative contribution of treatment side-effects and underlying disease. This study aimed to assess the prevalence of symptoms, their burden and the association with use of highly active antiretroviral therapy (HAART). Three hundred and forty-seven gay men with HIV disease completed an online survey, reporting data on age, CD4, viral load, year of diagnosis, HAART use, and the Memorial Symptom Assessment Scale Short Form (MSAS-SF).Those men currently receiving HAART (n=210, 56.6%) reported a higher number of symptoms than those without (14 versus 10.3, P=0.001). Fourteen physical symptoms were significantly more frequent among HAART users. Symptoms of psychological distress were the most common in both groups, ranging from 69.2% to 79.5%. Mean distress indices were higher for those on treatment with respect to both global (P=0.011) and physical (P=0.001) distress. In multivariate analysis, use of HAART was independently associated with number of physical symptoms (b=2.81, P=0.006), and physical distress score (b=2.45, P=0.017); both increasing with HAART use when controlling for age, year of diagnosis, CD4 and viral load. The high symptom prevalence, particularly psychological symptoms, is comparable with end-stage malignant and non-malignant diseases. Greater attention needs to be paid to the assessment and management of burdensome symptoms.