Multivariate linear regression analyses were used to define the relations of water levels in the Upper Floridan aquifer (UFA) and surficial aquifer system (SAS) to anthropogenic and meteorological stressors between 1995 and 2007 at two monitoring well sites (Charlotte Street and Lake Oliver) in east-central Florida. Anthropogenic stressors of interest included municipal and agricultural groundwater withdrawals, and application of reclaimed-water to rapid-infiltration basins (source of aquifer recharge). Meteorological stressors included precipitation and potential evapotranspiration. Overall, anthropogenic and meteorological stressors accounted for about 40 to 89 percent of the variance in UFA and SAS groundwater levels and water-level changes. While mean monthly water levels were better correlated with monthly stressor values, changes in UFA and SAS water levels were better correlated with changes in stressor values. Water levels and water-level changes were influenced by system persistence as the moving-averaged values of both stressor types, which accounted for the influence of the previous month(s) conditions, consistently yielded higher adjusted coefficients of determination (R2 adj) values than did single monthly values. While monthly water-level changes tend to be influenced equally with both stressors across the hydrologically averaged 13-year period, changes were more influenced by one stressor or the other seasonally and during extended wet and dry periods. Seasonally, UFA water-level changes tended to be more influenced by anthropogenic stressors than by meteorological stressors, while changes in SAS water levels tended to be more influenced by meteorological stressors. During extended dry periods (12 months or greater), changes in UFA water levels at Charlotte Street were more affected by anthropogenic stressors than by meteorological stressors, while changes in SAS levels were more affected by meteorological stressors. At Lake Oliver, changes in both UFA and SAS water levels were better correlated with meteorological stressors for all but the wet period between April 1995 and April 1996. Interestingly, changes in both UFA and SAS water levels at Charlotte Street were also better correlated with anthropogenic stressors during a similar wet period between April 1995 and June 1996 when substantive reductions in groundwater withdrawals resulted in appreciable recovery of both UFA and SAS water levels. The regional effects of anthropogenic stressors had limited influence on water-level changes at Charlotte Street and virtually no influence on changes at Lake Oliver. When regressed against the 2.2 Mgal/d (million gallons per day) of municipal withdrawals located within 2 miles of the Charlotte Street site, water-level changes were influenced solely by precipitation and potential evapotranspiration. At a radius of 2.5 miles, however, where cumulative withdrawals totaled about 9.5 Mgal/d, water-level changes were equally influenced by both anthropogenic and meteorological stressors. Withdrawals located at distances of greater than 3 miles from this site had no appreciable effect on relations between water-level changes and these stressors. At Lake Oliver, changes in UFA water levels were equally influenced by both stressors regardless of distance, while changes in SAS levels were more influenced by meteorological stressors at all distances.