AIMS: To study in vivo human lens epithelial cell proliferation on the anterior surface of PMMA implants and its interaction with postoperative blood-aqueous barrier breakdown in eyes undergoing cataract surgery. METHODS: A prospective study was carried out on three consecutive patient cohorts undergoing cataract surgery with intraocular lens implantation using three different surgical techniques which produce different anatomical relations between the implant and lens capsule. Specular microscopy of the anterior implant surface was used to document the natural history, topography, and density of lens epithelial cells and the laser flare and cell meter were used to measure postoperative blood-aqueous barrier breakdown. RESULTS: All groups showed lens epithelial cell proliferation onto the anterior surface of PMMA implants. This was initiated by and restricted to the region of anterior capsule-implant contact and decreased with the onset of anterior capsular opacification. Significant correlation was found in all groups between lens epithelial cell proliferation and postoperative blood-aqueous barrier breakdown. CONCLUSIONS: Human lens epithelial cell behaviour on PMMA surfaces in vivo differs from that seen in culture studies. Humoral factors in the aqueous, biomaterial properties of the implant, and its anatomical relations with the anterior and posterior lens capsule influence lens epithelial cell behaviour in vivo.