OBJECTIVE: To examine whether human retrovirus-5 (HRV-5) infection is associated with Sjogren\'s syndrome. METHODS: Salivary gland DNA was tested by nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Rigorous precautions were taken to prevent false-positive results from PCR contamination. Positive samples were confirmed by testing with an additional independent set of primers and were then sequenced. RESULTS: Ninety-two samples were examined (55 from Sjogren\'s syndrome patients, 37 from non-Sjogren\'s syndrome patients), 2 of which were positive. One was from a patient who had sicca symptoms but who did not satisfy the criteria for a diagnosis of Sjogren\'s syndrome. The other was from a patient with secondary Sjogren\'s syndrome. Owing to the extremely low virus load in minor salivary glands, the number of HRV-5-infected patients may be underestimated. In total, 3 different sequences of HRV-5 were identified which were 98% identical to the original sequence but which displayed variations between and within individuals. CONCLUSION: This is the first study to systematically seek a disease association with HRV-5, although with this method, an association with Sjogren\'s syndrome was not identified.