A laboratory study was conducted to evaluate the Panavia 21 resin-based adhesive system as a bonding agent between a variety of dental substrates. Panavia 21 resin was bonded directly to enamel and dentin and placed between nickel-chromium-beryllium (Ni-Cr-Be) specimens and enamel, dentin, other Ni-Cr-Be samples, and type III gold. Panavia 21 resin was also used to bond amalgam to dentin. Shear bond strengths were determined at 24 hours and after thermocycling at 3 months. The results of this study at both the 24-hour and the 3-months test periods indicate that the enamel bond strengths of Panavia 21 resin (24 hours, 19.3 +/- 5.5 MPa; 3 months, 23.7 +/- 4.4 MPa) exceeded its dentin bond strengths (24 hours, 7.8 +/- 1.4 MPa; 3 months, 8.8 +/- 3.2 MPa). The bond strengths between Panavia 21 resin and Ni-Cr-Be alloy (24 hours, 16.3 +/- 3.4 MPa; 3 months, 17.6 +/- 2.7 MPa) and those for Panavia 21 resin between Ni-Cr-Be alloy and dentin (24 hours, 18.7 +/- 4.2 MPa; 3 months, 19.8 +/- 5.3 MPa) were comparable to adhesive enamel bond strengths. High bond strengths were also generated by Panavia 21 resin between Ni-Cr-Be alloy and type III gold (24 hours, 39.3 +/- 5.9 MPa; 3 months, 35.5 +/- 7.1 MPa). The greatest bond strengths observed during both test time periods for Panavia 21 resin were between Ni-Cr-Be alloy and enamel (24 hours, 54.2 +/- 10.7 MPa; 3 months, 56.4 +/- 7.1 MPa) and between two samples of Ni-Cr-Be alloy (24 hours, 55.1 +/- 5.6 MPa; 3 months, 49.1 +/- 8.6 MPa). Panavia 21 resin produced high bond strengths between a variety of dental substrates commonly used for the placement of fixed prosthodontic restorations.