In the context of understanding the properties of model lung surfactant systems, surface phase behavior of spread monolayers containing mixtures of dipalmitoylphosphatidylcholine (DPPC), with various unsaturated phosphatidylcholine (PC) and phosphatidylglycerol(PG) derivatives, has been determined using surface pressure area isotherms on Tris buffer (pH 7.4, 15 mM NaCl) and fluorescence microscopy. DPPC, at all surface pressures below collapse, is completely miscible with dipalmitoylphosphatidylglycerol and with 1-palmitoyl-2-oleoylphosphatidylcholine dioleoylphosphatidylcholine up to mole fractions of at least 0.70 DPPC. On the other hand, DPPC is partially immiscible at mole fractions of 0.50 and greater when mixed with 1-palmitoyl-2-oleoylphosphatidylglycerol and dioleoylphosphatidylglycerol, with immiscibility increasing as the surface pressure is increased and with the replacement of 15 mM NaCl of the buffered subphase by 5 mM Ca2+. The substitution of one unsaturated acyl chain into PO appears to produce phase separation equivalent to that produced by two saturated acyl chains of PG with about four carbons less than saturated acyl chains of DPPC. When DPPC/unsaturated PG mixtures are considered in model lung surfactant studies or as artificial lung surfactant systems, such strong tendencies for surface phase separation may be important and should be taken into account.