FK-506 is a new immunosuppressant with the ability to inhibit activation of T-lymphocytes that would be cytolytic to an allograft. We studied periocular injection of FK-506 in a rat penetrating keratoplasty model. Corneas were transplanted from Brown Norway rats into Lewis rat recipients. The transplanted rats received periocular injection of either 0.5 mg/kg FK-506 or an equivalent volume of FK-506 vehicle only. Injections were given 1 day before, at keratoplasty, and every other day after keratoplasty until allograft rejection. The group receiving FK- 506 had a significant delay in allograft rejection (p < 0.05). The FK-506 group rejected 12-20 days postkeratoplasty with a mean rejection time (MRT) of 14.3 days, compared with 8-14 days (MRT 11.1 days) for the control group. We conclude that periocular administration of FK- 506 is effective in prolonging allograft survival in the rat penetrating keratoplasty model.