Scanning electron microscopy was used to evaluate the corneal epithelium of rabbit eyes after administration of two preservative-free ocular lubricants, preservative-free artificial tear-1 (Hypotears PF) and preservative-free artificial tear-2 (Refresh), and 0.02% benzalkonium chloride. Animals were randomly assigned to either mild or exaggerated use regimens. A quantitative rating system was used to assess epithelial damage. With mild use, scanning electron microscopy revealed normal epithelial morphologic characteristics for both preservative-free artificial tear solutions (mean relative damage score, solution 1, 0.75 +/- 0.16; solution 2, 1.02 +/- 0.23), which were not significantly different from eyes treated with phosphate-buffered saline (1.38 +/- 0.38) or a mild dosage regimen of 0.02% benzalkonium chloride (1.20 +/- 0.12). Exaggerated use with preservative-free artificial tear solutions (solution 1, 1.31 +/- 0.21; solution 2, 1.35 +/- 0.08) induced minimal damage that was not different from control eyes treated with phosphate-buffered saline (1.26 +/- 0.13). Compared with an exaggerated use of 0.02% benzalkonium chloride (4.0 +/- 0.16), both preservative-free artificial tear solutions induced significantly less epithelial damage (P = .0001). These results suggest that with frequent-dosage regimens, preservation-free artificial tear solutions-1 and -2 are free of the toxic effects associated with preserved solutions.