BACKGROUND: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease affecting people of various ages across the globe. Treatment for the disease is in the form of immunosuppressive drugs. Due to either the treatment of the disease or the disease itself, SLE patients have been shown to have abnormal immune function. This dysfunction accounts for an increased rate of infections in this population. Reactivation of the varicella zoster virus (VZV), herpes zoster (HZ), has been shown to occur in the SLE population at higher rates than the general, healthy population. Recently a vaccine for HZ was approved by the Food and Drug Administration for individuals 50 years of age and older. STUDY: In this study we examined the safety and immunogenicity of the HZ vaccine, Zostavax, in a small sample of SLE patients. This study was a case-control with a ratio of 1:1, SLE patients to healthy controls. The total sample size was 20 with an average age of 57.9. All study participants were seen in a clinical setting at the Oklahoma Medical Research Foundation and signed informed consents. Subjects were seen for an initial baseline visit, and were administered the vaccine. Follow-up visits were scheduled at 2, 6 and 12 weeks. RESULTS: The notable finding of this study is a lack of significant differences between SLE patients and healthy individuals with one exception. At the 6-week point a significant difference was found (P=0.03) between SLE patients and healthy controls, with regards to the number of VZV-specific cells stimulated to produce interferon gamma. No vaccine-induced illness was evident and there was no sign of an increase in SLE disease activity in patients.