Newnans, Lochloosa, and Orange Lakes are closely hydrologically connected karst lakes located in north-central Florida, United States. The complex karst hydrology in this region poses a great challenge to the hydrological modeling that is essential to the development of Total Maximum Daily Loads for these lakes. We used a Hydrological Simulation Program -Fortran model coupled with the parallel Parameter ESTimation model calibration and uncertainty analysis software to estimate effectively the hydrological interactions between the lakes and the underlying upper Floridan aquifer and the water budgets for these three lakes. The net results of the lake-groundwater interactions in Newnans and Orange Lakes are that both lakes recharge the underlying upper Floridan aquifer, with the recharge rate of the latter one magnitude greater than that of the former. However, for Lochloosa Lake, the net lake-groundwater interaction is that the lake gains water from groundwater in a significant amount, approximately 40% of its total terrestrial water input. The annual average vertical leakages estimated for Newnans, Lochloosa, and Orange Lakes are 6.0 · 10 6 , )8.9 · 10 6 , and 44.4 · 10 6 m 3 , respectively. The average vertical hydraulic conductance (K v ⁄ b) of the units between a lake bottom and the underlying upper Floridan aquifer in this region are also estimated to be from 1.26 · 10 )4 to 1.01 · 10 )3 day )1 .(KEY TERMS: HSPF; karst hydrology; lake water budget; optimization; surface water ⁄ groundwater interaction.)