Aim. Despite the prevalence of HIV and AIDS in South Africa reaching pandemic proportions, very few studies have been published on co-morbid depression. This study at Chris Hani Baragwanath Hospital was conducted on a group of HIV-positive patients with depression who were receivingantiretroviral treatment. The aim of the study was to describe their response to treatment with either an antidepressant or psychotherapy.Method. The study was prospective, randomised and controlled. The sampling was a convenience sampling, as it included patients attending the HIV clinic. At entry to the study, a clinical diagnostic evaluation and the Hamilton Depression Rating Scale (HAMD) were performed on all subjects by the investigator. The depressed patients were randomly assigned to receive either an antidepressant (citalopram) or psychotherapy (interpersonal psychotherapy, IPT). The HAMD was repeated at the study endpoint of 8 weeks.Results. Sixty-two HIV-positive persons receiving antiretrovirals participated in this study. Thirty of them were not depressed and served as controls, and 32 were depressed. There were no significant differences between the controls and the patients (either receiving pharmacotherapy or psychotherapy) in respect of any of the socio-demographic characteristicsevaluated (p>0.05). Approximately 60% (n=19) of the depressed patients were, randomised to receive pharmacotherapy, while 40.6% (n=13) received IPT. The mean HAMD scores of the patients on pharmacotherapy decreased from 25.7 to 6.2 from entry to completion of the study, and those for patients receiving psychotherapy decreased from 22.5 to 8.2. The decreases in HAMD scores in patient groups receiving either pharmacotherapy or psychotherapy were not significantly associated with any socio-demographic variables (p>0.05).Conclusion. Both pharmacotherapy and psychotherapy may be equally effective in the treatment of depression in HIV-positive patients. The choice of treatment will be influenced by factors such as adverse effects of antidepressants and adding another medication to an already complex antiretroviral regimen. In such cases, IPT may be particularly beneficial.