BACKGROUND: Necrotizing retinopathies of suspected viral origin, but which do not meet the criteria for either CMV-retinitis or acute retinal necrosis syndrome, have been grouped together under the term atypical necrotizing retinopathies. Nothing is known about their etiology. PATIENTS AND METHODS: Aqueous humor samples were drawn from two HIV-positive and eight patients with AIDS presenting with an atypical necrotizing retinopathy, additionally from six patients with acute retinal necrosis syndrome and 28 patients with active CMV-retinitis at the time of diagnosis as well as from thirty healthy controls at surgery. All samples underwent DNA extraction and amplification for viral DNA of HSV-1, VZV and CMV. RESULTS: VZV-DNA was detected in seven of nine aqueous humor samples derived from patients with atypical necrotizing retinopathies and in four of six samples from patients with acute retinal necrosis syndrome, but not in any one from the 28 patients with CMV retinitis. In the latter group, CMV DNA was detectable in 23 samples, in two of these additionally HSV-1 DNA. No viral DNA was amplified from any of the samples from healthy controls. CONCLUSIONS: Varicella zoster virus ist the leading cause of atypical necrotizing retinopathies. This should be considered in the antiviral chemotherapy. Moreover, we were able to establish the diagnosis using DNA amplification for the viruses of the herpes family irrespective of the etiology in 80% of necrotizing retinopathies.