To evaluate the effect of epinephrine on the cellular proliferation and production of nitric oxide (NO) in trabecular meshwork (TM) cells, cultured porcine TM cells were exposed to epinephrine at various concentrations, with and without its NO inhibitor, N^ω -Nitro-L-arginine methyl ester (L-NAME). The proliferation of TM cells and the production of NO were quantified by rapid colorimetric assays. Acridine orange/Hoechest 33342 staining and flow cytometry were done to evaluate apoptosis. Epinephrine inhibited the proliferation of cultured TM cells and produced NO at significant levels in a dose-dependent manner. However, the antiproliferative effect of epinephrine was abolished by L-NAME. Fluorescent microscopy and flow cytometric analysis revealed that epinephrine induced apoptotic cell death, which was suppressed by L-NAME. The current results suggest that the inhibitory effect of epinephrine on TM cell survival is associated with NO production. NO-mediated apoptosis may be involved in this epinephrine-induced antiproliferative effect on TM cells.