Debonding and premature failure of prosthetic–polymethylmethacrylate interfaces have been shown to be exacerbated by exposure to physiological environment. In efforts to counteract these hydrolytic degradation effects, two clinically relevant Co-Cr-Mo surface morphologies were treated with an organosilane adhesion promoter (γ-methacyloxypropyltrimethoxy) before interface bonding. Samples were quantitatively characterized in terms of the adhesion (fracture) and subcritical debond growth-rate (fatigue) behavior of the interface. The steady-state interface debond resistance, Gss (J/m2), was shown to increase with application of the silane pretreatment both in air (20°C, 45% relative humidity) and simulated physiological environment (37°C, Ringer's). Similarly, positive shifts in the subcritical debond threshold, ΔGTH, values are observed for silane pretreated interfaces. A shift in the debond path from primarily adhesive failure in untreated surfaces to cohesive failure between the silane layer and bulk polymethylmethacrylate for silane treated surfaces was observed. Silane pretreatment of Co-Cr-Mo surfaces was shown to effectively limit the degree of the environmental degradation. General insights to the effects of surface roughness, chemical enhancement, and the environmental effects on the thermodynamics at the interface and resulting debond behavior are discussed. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res 54: 419–427, 2001