The amphiphilic mixed-substituent polyphosphazenes, [NP(OCH2CF3)x (NHCH3)y)]n and [NP(OC6H5)x (NHCH3)y]n, have been prepared by the sequential replacement of chlorine in [NPCI2]n by trifluorethoxide or phenoxide and methylamine. Thin films of these species were cross-linked by exposure to gamma radiation and the semipermeability of the resultant membranes was monitored. The radiation-induced cross-linking and membrane-forming properties of these polymers were compared with those of the single substituent polymers, [NP(OCH2CF3)2]n, [NP(OC6H5)2]n, and [NP(NHCH3)2]n. The radiation-cross-linking and appeared to involve free radical reactions at the methyl groups of the methylamino substituents. The possible utility of these materials in biomedical research is discussed.