The proposed HIV, AIDS and Tuberculosis (TB) research training program builds on the successes and lessons of the previous 10 years. The growing research infrastructure, the growing local HIV, AIDS and TB scientific expertise and capacity to undertake research across a continuum from basic science, clinical, epidemiological and social science research creates a new set of challenges and opportunities for this hitherto successful training program. The evolving HIV, AIDS and TB epidemics and the growing local science base and collaborations with leading US scientists require some adaptation of the program to meet the existing and emerging research training needs in South Africa and the region. The past 44 long-term and 69 short-term trainees of the program have been scientifically productive (515 publications including papers in Science, Nature, and Lancet), have made major new scientific contributions in HIV, AIDS and TB. They have been instrumental to South Africa's success in securing pivotal NIH and other international HIV and TB grants and have taken up several key leadership positions in these fields. The continuum of HIV, AIDS and TB training, research, and mentoring between the US and SA in the previous funding cycles have already gone some way towards equalizing the partnership between the US and South Africa. More still needs to be done, especially as the challenge of training for AIDS treatment provision and AIDS treatment program evaluations becomes more immediate and with the growth in MDR TB and the emergence of XDR TB. The emphasis of the program in this current cycle will be to identify critical gaps in existing centers of HIV, AIDS and TB research excellence in South Africa and recruit, train and mentor appropriate enthusiastic, bright young and established mid-level investigators to provide them with the knowledge base and skills needed for the design and conduct of large-scale clinical trials (esp for HIV vaccines, microbicides, new TB diagnostics and drugs); Clade C pathogenesis studies, studies on the HIV/TB interaction and evaluation of the impact of ARV treatment. The goal is to strengthen existing and expand the number of independent HIV and TB research teams in South Africa; strengthen South Africa's capacity to assume more of the country's and region's HIV, AIDS and TB training needs and developing the skills needed to operationalize, implement and monitor the South African scale-up of AIDS treatment. Guided by the ongoing assessment of training priorities and with careful oversight from a balanced US-SA Scientific Advisory Committee, we will continue to provide as appropriate a variety of short-to-medium, and long-term HIV, AIDS and TB research training opportunities in the US and South Africa. Priority will be given to trainees from recognized HIV/AIDS and TB research groups. Vigorous effort will go towards equalization of the training opportunities between the US and South Africa. This includes the establishment of a high quality masters program in epidemiology in South Africa taught initially jointly by US and South African faculty. A rich tapestry of AIDS and TB projects funded by NIH, CDC, and others offer diverse training and research opportunities to trainees for their placements. Overall, this program is designed to increase the number of independent established AIDS and TB researchers in South Africa so that there is local critical mass for future in-country mentorship and training. While this is a long-term goal, the proposed program sets about this task well armed with the most valuable lessons learnt in the last 5 years such as the importance of ongoing in-country mentorship, guidance and support, assistance with grant writing, and recruitment of candidates who are already in productive HIV, AIDS and TB research groups. [unreadable]