T-20 is a novel antiretroviral agent that inhibits the fusion of human immunodeficiency virus (HIV) with target cell membranes. It is delivered by self-administered, twice-daily, subcutaneous injections. The impact of this mode of administration on patients' ability to conduct normal activities of daily living (ADL) and comply with a T-20 treatment regimen was assessed as part of a 48-week, phase 2 trial (T20-205). Patients' opinions on the impact of T-20 on ADL, ease of use of T-20, and choice to continue with T-20 were assessed by two questionnaires completed at baseline and week 48 (or study withdrawal). ADL were measured using a Likert-type scale based on established instruments with questions added to assess HIV-specific issues. Seventy previously treated patients received T-20 in combination with an average of five oral antiretroviral agents. Relative to other HIV/AIDS drugs, T-20 had little impact on ADL, with the majority of patients (54%-96%) agreeing (somewhat or strongly) that subcutaneous injections had not limited ADL. Patients found the injections relatively easy to perform with more than 47% of patients stating that each aspect of the injections (ease of injection, storage, reconstitution, and disposal of sharps) were very easy or easy. If medically indicated, 98% of patients stated that they would choose to continue with T-20. The most common reasons for this were the perceived effectiveness of T-20 and lack of side effects. In conclusion, the need to deliver T-20 via twice-daily subcutaneous injections was not considered an important barrier by HIV-positive patients seeking improvement or stabilization of their condition.