Objective: The aims of this study were to investigate the stability of depressive symptoms over time, explore possible reasons for the genesis of depressive symptoms, examine psychosocial adjustment over time and examine the effects of the introduction of highly active antiretroviral therapy (HAART) in a group of HIV infected patients. Method: HIV seropositive outpatients were assessed at 6 monthly intervals over a 2-year period. At each assessment patients completed the Beck Depression Inventory, the Life Event Inventory, the Core Bereavement Item questionnaire and the Psychosocial Adjustment to Illness Scale. Details regarding HIV illness progression and antiretroviral treatment were recorded for each follow-up assessment. Results: One hundred and sixty-three patients completed the baseline assessment and proceeded to the 2-year follow-up study. Most patients remained well over the 2-year follow-up period; mean CD4 count for the group increased over the study period. Ten patients developed AIDS and 18 patients died. Antiretroviral medications changed significantly during the follow-up, with most patients changing to combination (triple) therapy, which included the use of a protease inhibitor. Psychosocial stressors (life event distress and number of bereavements) reduced as the study progressed. Reported depressive symptoms decreased over time and psychosocial adjustment to illness tended to improve over the 2-year period. Conclusions: Over a 2-year follow-up period HIV/AIDS symptoms and illness markers and psychosocial adjustment to illness improved, psychological stressors and depressive symptoms decreased, with a temporal relationship to changes in antiretroviral therapy.