Critiques of biomedical research in low-resource settings typically centre on clinical trials and the 'dissymmetries of power' between the researched and those benefiting from the products of research. It is important to extend this critical lens to other forms of global health research. We conducted a qualitative study in Tanzania to explore meaning and experiences of participating in a clinical observational study evaluating the safety and efficacy of current practice for treating HIV and malaria co-infection. Focus group discussions and in-depth interviews were undertaken with 124 study participants, study staff and health workers. Participants' understanding of the study's research aims was limited, but the practice of participation - engaging with research staff and materials - appeared to facilitate interpretations of the study's value, conceptualised as a 'service'. For those peripheral to the study, however, interpretations of it reflected existing suspicions of experimental research. Our findings indicate the importance of considering the expectations, roles and responsibilities constructed through the practice of participation in different types of research, and how they relate to legacies of research. Understanding how networks of research practice intersect local social and historical contexts can extend discussions of collaboration and engagement with research in low-resource settings.