The purpose of this study was to determine the effect of contact lens wear on the tear film and ocular surface of people tolerant or intolerant to contact lens wear. Twenty subjects participated; 11 tolerants and nine intolerants. Their baseline tear film (no lens wear) was analysed with a range of clinical measurements and protein analyses (lactoferrin, sIgA and lysozyme). The tests were then repeated at the end of 6h of contact lens wear during the day and while lenses were worn. Both tolerants and intolerants showed statistically significant increases in bulbar and overall conjunctival redness after 6h of lens wear. For tolerants only, there was a statistically significant increase in the tear film meniscus area (0.08 mm(2) +/- 0.04 compared to 0.14 mm(2) +/- 0.06 (p = 0.023)) and a statistically significant decrease in the non-invasive tear film break-up time (NI-TBUT; 21.3 s +/- 5.7 compared to 3.7 s +/- 4.3 (p = 0.003)) after 6h of lens wear. There were no changes in other tear film or ocular surface parameters. The protein concentration and lipid layer appearance did not change during lens wear for either population. Prior to lens wear, tolerant subjects had a statistically longer NI-TBUT, higher phenol red thread test and higher tear flow rate. After 6h of lens wear and while wearing lenses, all but NI-TBUT remained statistically different. Lens wear affected only a small number of clinical variables and 6h wear did not effect the concentration of those proteins measured in tears in this study.