Cellular adaptation to elevated alcohol concentration involves altering membrane lipid composition to counteract fluidization. However, few studies have examined the biophysical response of biologically relevant heterogeneous membranes. Lipid phase behavior, molecular packing, and elasticity have been examined by surface pressure-area (pi-A) analysis in mixed monolayers composed of saturated dipalmitoylphosphatidylcholine (DPPC) and unsaturated dioleoylphosphatidylcholine (DOPC) as a function of DOPC and n-butanol concentration. n-Butanol partitioning into DPPC monolayers led to lipid expansion and increased elasticity. Greater lipid expansion occurred with increasing DOPC concentration, and a maximum was observed at equimolar DPPC:DOPC consistent with n-butanol partitioning between coexisting liquid expanded (LE, DOPC) phases and liquid condensed (LC, DPPC) domains. This led to distinct changes in the size and morphology of LC domains. In DOPC-rich monolayers the effect of n-butanol adsorption on pi-A behavior was less pronounced due to DOPC tail kinking. These results point to the importance of lipid composition and phase coexistence on n-butanol partitioning and monolayer restructuring.