An important implication of the estimated 1,600 new HIV infections occurring per day in South Africa are the rising costs and increasingly complicated logistics associated with existing laboratory methodologies for the surveillance, diagnosis and monitoring of HIV and associated infections. Importantly, the arrival of free or affordable antiretroviral medications in South Africa is imminent, but the ability to affordably diagnose and monitor HIV infection in the laboratory remains an obstacle to national implementation of antiretrovirals. While there is a need to identify more feasible technologies for the monitoring of disease, these must be shown to be equivalent to the existing developed world standards in effectiveness. The Innovative HIV/AIDS Diagnostic and Monitoring project is divided into four sections; natural history, molecular epidemiology, genetics and innovative surveillance, diagnostic and monitoring assays. The aim is to develop innovative, rapid and inexpensive systems for epidemiological surveillance (disease, molecular and community) and individual diagnostic HIV and opportunistic infections testing and monitoring. This project encompasses field assessment and implementation of simple and easy to use surveillance tests and sample collection methodologies to expand existing infection and disease surveillance and molecular epidemiological systems and thus allow for the accumulation of essential baseline human immunodeficiency virus (HIV) virological and South African population genetic information. The largescale use of innovative sample collection methods for HIV surveillance such as dried blood spots and oral fluid or whole blood rapid HIV tests has not yet been done in South Africa. Furthermore, this project will develop and validate affordable alternative testing systems (CD4 counts, viral loads, heat denatured and imrnune-complexed p24, immune monitoring, resistance testing) that can be used as accurate alternatives to existing but more expensive diagnostic and monitoring tests. If implemented these novel sample-collecting techniques will decrease the potential risks of exposure to bio-hazardous material of health care staff and patients and could ensure a more feasible HIV laboratory service. The human subjects enrolled in the other projects will benefit directly from the diagnostic and monitoring information generated by the laboratory projects described here.