Objective: The aim of this study was to examine the association between medication exposure and (1) unstimulated whole-salivary flow rate and (2) the severity of xerostomia among older people while adjusting for multiple medication use. Methods: Data were obtained from participants remaining at the five-year follow-up phase of a cohort study of community-dwelling older South Australians. Medication exposure information was available at baseline and at five years, enabling examination of the effects on dry mouth of long-term exposure to medications. At the five-year follow-up, unstimulated salivary flow was estimated using the spit method, and xerostomia severity was estimated using the 11-item Xerostomia Inventory. Because of the potential difficulties posed by polypharmacy, a two-stage analytical approach was employed: (1) Classification and Regression Tree (CART) analysis was used as an exploratory device to elucidate the relationships among the dependent and independent variables, and (2) linear regression analysis was used as a complementary procedure. Results: Unstimulated flow rate was lower among individuals who were female or taking antide-pressants at both baseline and five years, and higher among smokers or people who were taking hypolipidemic drugs. Xerostomia severity was higher among females, or individuals taking: (1) an anginal at baseline and five years, (2) an anginal without a concomitant betablocker at five years, (3) thyroxine and a diuretic at five years, or (4) antidepressants or antiasthma drugs at both baseline and at five years. Conclusions: These results suggest that polypharmacy can be accounted for to a certain extent by using CART analysis in conjunction with more conventional approaches; and that the relationship between medications and dry mouth is a complex one, and differs according to which aspect of dry mouth is being examined.