HIV-associated salivary gland disease (HIV-SGD) is characterized by enlargement of the major salivary glands and/or xerostomia. HIV does not appear to play a direct role in this disease since it was detected by immunohistochemistry in only occasional lymphocytes in labial salivary glands in two out of six patients; it was not found in the salivary gland epithelial cells. Moreover, HIV was not found in any of 21 saliva samples from seven patients. We conclude that HIV-SGD is not caused by direct infection of the salivary glands with HIV.