SS patients are characterized by decreased volume of lacrimal and salivary secretions. The dryness results from a combination of destroyed glandular elements as well as by interference with the neuro-endocrine innervation of the residual glands. Specific genetic factors (i.e. HLA class II alleles) have been associated with increased risk of SS in Caucasian (US), Chinese and Japanese populations. However, different class II MHC alleles are risk factors in each population. The environmental factors that precipitate SS remain unknown. Future understanding of the mechanisms of destruction of the salivary and lacrimal glands may provide a more rationale approach to therapy.