Molecular dynamics simulations in which the number of molecules (N), the two-dimensional pressure (pi), and the temperature (T) are held fixed (N pi T) were performed on phospholipid monolayers in two-dimensional periodic boundary conditions. Four different phospholipids were simulated : dipalmitoylphosphatidylcholine (DPPC), disteroylphosphatidylethanolamine (DSPE), 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), and 1-steroyl-2-arachidonylphosphatidylethanolamine (SAPE) in both low- and high-density states. The simulations reproduced pressure- area isotherms measured on a Langmuir-Blodgett trough. The alkyl chain alignment in the low-density simulations also compared well to results of H-2 NMR investigations from the Literature. Simulations in which the area of the lipid monolayer was fixed (NAT) were also performed. Simulations in the N pi T ensemble were superior to the NAT simulations. Inaccurate equilibrium pressures and alkyl chain order resulted from the NAT simulations. Experimental results indicated the presence of a phase transition in the DPPC isotherm. The simulations indicate this phase transition results from a desolvation of the lipid headgroups as the monolayer is pressurized. However, these simulations have not completely equilibrated. This makes any conclusions drawn from these or the many similar simulations in the literature suspect until independent validation is obtained.