An oligomeric isocyanate, poly[methylene(phenylene isocyanate)] (PMPI), is demonstrated to be an efficient reactive compatibilizer for blends of polyamide-6 (PA6) and poly(2,6-dimethyl-1,4-phenylene ether)(PPE). Use of this compatibilizer results in substantial improvements in mechanical properties. The multiple functional isocyanate acts as a coupling agent and reacts with PA6 and PPE endgroups during melt processing to produce a PA6-co-PMPI-co-PPE mixed copolymer at the interface. This in situ-formed copolymer tends to reside at the interface to reduce the melt interfacial tension and enhance interface adhesion.