OBJECTIVE: The objective of this qualitative study was to explore how clinical symptoms may affect adherence to antiretroviral therapy (ART) in HIV patients, and to explore factors, perceptions and attitudes related to adherence to therapy. DESIGN: A qualitative study was carried out in the context of the prospective cohort study "Evaluation of Immune Reconstitution Following Initiation of Highly Active Antiretroviral Treatment in Manhica, Mozambique". In-depth Interviews were conducted twice in a sub-sample of the study cohort (51 participants), at six-month intervals. RESULTS: Most participants (73%) knew that AIDS is a chronic disease and that ART does not cure it. Nine participants (18%) were non-adherent at some point and two (4%) abandoned ART. All participants but five reported having symptoms after starting ART, mainly attributed to pills needing time to act and body's reaction to the treatment. In spite of the perceived severity of the symptoms, only two people reported they discontinued the treatment due to symptoms. Almost all participants reported feeling comfortable with the HIV clinic organization and procedures, but afraid of staff being hostile if they did not follow the rules or if the health worker visited their home. Family was one of the most important source of support according participants. Almost all participants with children said that a decisive factor to follow the treatment was the desire to be able to look after them. CONCLUSIONS: Experiencing symptoms after starting treatment was not a barrier to adherence to ART. Factors related to adherence included control measures set up by the health facility (exhaustive follow up, support, information) and family and community support. Indirect ART-related expenses did jeopardise adherence.