The aim of this in vitro study was to do a morphological comparison of tooth/composite interface by means of three composite systems: (1) a specific formulated primer adhesive and Organically Modified Ceramics (ORMOCER) composite, (2) an universal self-etching adhesive and the same ORMOCER composite, (3) and the same universal adhesive used for Group 2 and a fine-particle hybrid resin composite. The rational for this study was based on the recommendations from manufacturers that nonspecific dentin bonding agents can be used with ORMOCER. Twenty-one Class II cavities were prepared in extracted third molars. Seven randomly assigned teeth were restored with one of the three methods according to the instructions provided by the manufacturer. Following completion of the restorations, the teeth were sectioned and evaluated by means of scanning electron microscopy for evaluation of interfacial morphology and light microscopy for the determination of microleakage. The last was scored as being present or absent. The best results were observed using method 1, in which a special primer adhesive and ORMOCER composite was used. In this group there were statistically significant fewer gaps in enamel (4.7+/- 7.5%) and dentin (22.8 +/- 7.4%) compared to the other two groups (Group 2: enamel 21.1 +/- 8.3% and dentin 66.3 +/- 17.3%; and Group 3: enamel 40.6 +/- 35.2% and dentin 89.4 +/- 13.3%). The interfaceof method 2, universal self-etching adhesive and ORMOCER, was of a lesser quality than Group 1. Within the limitations of this study the recommendation is made to use the ORMOCER tested in this experiment with the matching specifically formulated primer adhesive system. A lack of adhesion as well as microleakage, were prominent features for Groups 2 and 3. From the data of this study the practitioner is cautioned not to indiscriminately exchange specific dentin bonding agents for nonspecific ones. Considering the shear endless number of possible combinations and the numerous different tests that would be required to test these all, selection of different combinations will remain a theoretical exercise.