The interdisciplinary field of psychoneuroimmunology (PNI), which aims to clarify the relationship between psychological factors and immunity, can also play a role in our understanding of individual susceptibility to, progression of immunologically mediated disease. Mechanisms proposed to account for the profoundly damaging effects of human immunodeficiency virus (HIV) on immune function do only partially explain the variability in individual rates of progression, suggesting, therefore, that other immunomodulatory factors are also involved. Studies have examined the proposal that the effects of stress and HIV may interact in some complex way, and psychological, physiological and virological evidence for the role of stress in HIV progression is discussed in detail. A critical review of HIV-specific research in PNI, which can be broadly divided into cross-sectional, longitudinal, and intervention studies, and studies of long-term survivors, reveals that the relationship between stress and HIV progression remains equivocal, because of limitations due to methodological difficulties and to our inadequate understanding of immunology and HIV. A model is proposed for the influence of psychosocial stress on progression in HIV disease, which takes account of some of these difficulties.