AIDS and systemic lupus erythematosus (SLE) share clinical and laboratory features that may difficult a differential diagnosis. We report five patients who presented diagnostic problems, two of them with SLE diagnosis and HIV-1 false-reactive screening tests, and the other three with AIDS diagnosis and clinical features fulfilling four or more ARA-clinical criteria for the diagnosis of SLE. It is recommended that tests for HIV-1 antibodies in patients with symptoms of SLE, be carried out by at least three different methods, with direct HIV-1 antigen detection as final confirmatory technique. On the other hand, as also proposed for Sjogren syndrome, the presence of HIV-1 or its antigens, established through cell-cultures or direct blood detection, should be considered as exclusion criteria for SLE diagnosis.