Several human lymphotropic herpesviruses have been found in certain lymphoproliferative disorders and implicated as possible etiologic factors or as modulating elements of the diseases. To assess a possible association of the human herpesviruses with lymphomas arising from mucosa-associated lymphoid tissue (MALT), we evaluated the presence of four human herpesviruses, Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), HHV-7, and HHV-8, in the biopsied specimens from 14 patients with primary ocular MALT lymphomas. EBV DNA sequences were detected in four specimens by polymerase chain reaction (PCR), and four cases were positive for HHV-6 DNA. In situ hybridization showed that three and two of 14 cases were positive for EBV mRNA and HHV-6 DNA, respectively. Neither HHV-7 nor HHV-8 sequences could be detected by PCR. These findings would stimulate further investigation as to the involvement of these lymphotropic viruses in the pathogenesis of a subset of low-grade primary ocular lymphomas.