Human epidermal growth factor (hEGF) plays a key role in the regulation of corneal epithelial regeneration. As the lacrimal concentration of EGF is known to decrease following corneal injury, therapeutic application of exogenic EGF to support corneal wound healing is currently being investigated. To evaluate the role of topical EGF substitution in perforating keratoplasty, the lacrimal secretion of EGF was determined in 12 patients prior to keratoplasty and on the 1st and 7th days postoperatively using a newly developed modular immunofluorometric assay. EGF secretion and tear-flow rates in the tear samples of the keratoplasty patients were compared with those of 39 patients with corneal epithelial defects of other origin and those of 21 healthy controls. Levels of EGF secretion and tear flow reflectorily increased both in the post-operative samples of keratoplasty patients (secretion 0.77 +/- 0.56 pg/s, tear flow 18.7 +/- 14.9 microliter/min) and in the samples of patients with corneal epithelial defects (0.6 +/- 0.4 pg/s, 19.6 +/- 19.2 microliter/min) in comparison with preoperative values and healthy controls (0.3 +/- 0.2 pg/s, 4.0 +/- 5.4 microliter/min). Men showed higher average levels of basal and reflectory EGF secretion (0.4 and 0.8 pg/s), respectively than did women (0.25 and 0.55 pg/s, respectively). The results indicate a physiological feedback mechanism that reflectorily adjusts the lacrimal EGF secretion following corneal irritation. Topical therapy with recombinant EGF should therefore be restricted to patients with persistent corneal epithelial defects and proven deficiency of EGF secretion.