Diagnosis of varicella-zoster virus (VZV) infection in immunocompromised patients is difficult because of the frequent atypical appearance. Accurate and early diagnosis is important to allow rapid commencement of antiviral chemotherapy, with consequent improvement in antiviral efficacy. A monoclonal based direct immunofluorescence antibody technique (VZV IFA) was assessed in parallel with viral culture in 56 patients with suspected VZV infection. A subgroup of 17 patients from this group with classical dermatomal herpes zoster all had positive VZV IFA tests. Only 6 patients (35%) were positive on viral culture. None of the 15 patients with proven herpes simplex virus infection had a positive VZV IFA, nor did any patient with positive VZV viral culture have a negative VZV IFA. The VZV IFA test is a rapid and sensitive technique for detecting infection with VZV.