A controlled, randomized, double-masked study was conducted on eight human subjects to determine the threshold level of hydrogen peroxide, which is toxic when introduced into the eye via a high water content (75%; Durasoft 4) hydrogel contact lens. Subjective comfort, conjunctival hyperemia, corneal and conjunctival epithelial staining, and corneal oxygen uptake were assessed in response to 5-min wear of lenses that were presoaked in isotonic saline solutions of physiologic pH containing 0, 25, 50, 100, 200, 400, and 800 parts per million (ppm) hydrogen peroxide. Higher levels of hydrogen peroxide were associated with greater discomfort (p less than 0.05) and increased conjunctival hyperemia (p less than 0.001). The highest level of hydrogen peroxide tested (800 ppm) did not induce significant corneal or conjunctival epithelial staining or alter the corneal aerobic response. We conclude that residual concentrations of hydrogen peroxide in contact lens care systems should not exceed 100 ppm. Practitioners can use these data to estimate the level of residual hydrogen peroxide to which a patient may have been exposed upon lens application after neutralization.