Latex versus glass has frequently been used as a model system for the investigation of natural lubrication mechanisms, despite its significant differences from articular cartilage pairings. The differences in surface chemistry account for its different behavior in terms of protein adsorption and lubrication. While cartilage is well known for its protein resistance, most proteins present in synovial fluid can non-specifically adsorb onto latex or glass. We have investigated latex-versus-glass lubrication by means of pin-on-disk tribometry in the presence of synovial-fluid proteins and glycoproteins, focusing on the influence of the glass-cleaning procedure on friction. In order to simulate the effects of possible contamination of glass in previous studies, both hydrophilic and hydrophobic glass substrates were tested. Albumin was shown to impair lubrication (in comparison to PBS) when latex was slid against both types of glass surface, whereas bovine synovial fluid (BSF) and alpha-1-acid glycoprotein (AGP) impaired the lubrication of latex versus hydrophilic glass and improved the lubrication of latex versus hydrophobic glass. Protein adsorption on the surfaces was monitored by means of fluorescence imaging and optical waveguide lightmode spectroscopy (OWLS), which revealed a faster and greater amount of adsorption of AGP on hydrophobic surfaces than on hydrophilic ones. The influence of surface chemistry on the friction behavior of BSF and on the adsorption of AGP suggests that it plays a role in determining the relative amounts of adsorbed synovial fluid proteins. When BSF is used as a lubricant in the latex-versus-hydrophobic-glass system, more of the AGP, relative to albumin, appears to adsorb on both surfaces, counteracting the negative effect of albumin on friction. It therefore seems that latex on glass, while displaying nominal similarities to cartilage on cartilage under certain conditions, is not a useful model system. Moreover, surface contamination of the glass can play a major role in determining the results.