The purpose of the study was to quantify the neuropeptide calcitonin gene-related peptide (CGRP) in normal human tear fluid and to determine the effect of photorefractive excimer laser keratectomy (PRK) on its release in tears. CGRP was assayed in tear fluid samples using an enzyme immunoassay (detection limit 0.2 micrograms ml-1). Tear-fluid samples were collected preoperatively, 1, 2 and 7 days after PRK and analysed for CGRP. The changes in tear-fluid secretion were also monitored. The intra-assay variation was 3.0-7.0%. Despite the marked hypersecretion of tears, the concentration of CGRP did not decrease following PRK indicating a concomitant increase in CGRP release by sensory nerves and/or lacrimal gland(s). Consequently, the release of CGRP in tears increased from 197.9 +/- 36.6 ng min-1 (mean +/- S.E.M.) to 1723.0 +/- 402.4 ng min-1 (P < 0.01) on day 1, and to 2304.2 +/- 561.1 ng min-1 (P < 0.01) on day 2. On day 7, only minor elevation (377.02 +/- 83.24 ng min-1) was observed. It is concluded that CGRP is a component of normal human tear fluid. The ocular irritation response related to the photoablation induces an enhanced release of CGRP in tears. As a compound present in corneal sensory nerves CGRP may have a role in wound-healing.