Corneal epithelial, stromal, and endothelial edema were assessed in 19 subjects before and after a 4-month period of hydrogel contact lens extended wear. A thick hydrogel lens was worn under closed-eye conditions for 3 hours to induce stromal edema and endothelial edema (blebs), and eye bathing with a hypotonic solution was used to induce epithelial edema. Initial central stromal edema (corneal thickness) was 14.4 +/- 0.6% in response to the stress lens compared with 2.1 +/- 0.4% in the control eye (mean +/- SE). After 4 months of lens extended wear, stromal edema was significantly reduced (P < 0.0001) to 12.3 +/- 0.6% and 0.5 +/- 0.2% in test and control eyes, respectively. Adjustment of the stromal edema response at the second visit for residual edema from the extended wear accounted for some of the reduction, but the edema response remained significantly decreased (stress lens: 13.6 +/- 0.7%; and control eye: 1.2 +/- 0.4%). Endothelial edema response to the stress lens, as measured on a scale of 1 to 7, decreased from 4.6 +/- 0.3 to 2.8 +/- 0.3 over the period of extended wear. The final level was indistinguishable from that of the eye not wearing the stress lens. The epithelial edema response to hypotonic exposure was not altered with extended wear. These findings indicate that the stromal and endothelial edema responses may be unreliable diagnostic signs of the physiologic impact of hydrogel extended wear.