3D-IPS/DFFT is an extension of the three-dimensional isotropic periodic sum (3D-IPS) for evaluation of electrostatic and Lennard-Jones interactions in heterogeneous systems; it utilizes a discrete fast Fourier transform (DFFT) for efficient calculation of the IPS potential with a large local region radius. The method is demonstrated to be highly accurate for simple bulk fluids, liquid/liquid and liquid/vapor interfaces, and lipid bilayers and monolayers. Values for r(C) (the cutoff distance for direct evaluation of pairs) and R-C (the local region radius) equal to 10 angstrom and twice the longest edge of the periodic cell, respectively, provide excellent efficiency and accuracy. Dimyristoylphosphatidylcholine (DMPC) monolayers simulated with the CHARMM (Chemistry at HARvard Molecular Mechanics) C27r lipid parameter set and 3D-IPS/DFFT yield Surface tensions approximately 8 dyn/cm higher than those simulated using particle mesh Ewald (PME), and with experiment. In contrast, surface tensions for DMPC bilayers are 16 dyn/cm/leaflet with both 3D-IPS/DFFT (r(C) = 10 and 12 angstrom) and PME (r(C) = 12 angstrom). This indicates that PME (r(C) = 12 angstrom) may be used for simulations of bilayers, but not monolayers, and that the large bilayer surface tension arising from C27r is incorrect.