Forty-five patients following penetrating keratoplasty (PK) were examined with the HRT III Rostock Cornea Module confocal microscope at various points after their surgery for two years. Activated keratocytes (AKs) were counted manually and their mean number evaluated. A pattern was noted where AKs number decreased steadily and stabilised by four months after PK in 39 patients without graft rejection. At one year, when post op steroid regimen was discontinued, there was a slight but significant increase in their number followed by continuing decline. During the first four months there were no significant differences in mean AKs counts between patients with and without graft rejection. In the six patients with graft rejection, the mean AK count was significantly higher than in patients without rejection, two months before, one month before, and at the rejection diagnosis. A pattern of increasing number of AKs starting at least two months prior to clinically visible rejection was noted. Although this study has a small sample and AK were counted manually, it proposes in vivo confocal microscopy as a useful tool in predicting graft rejection. Further study is needed to evaluate if increasing steroidal therapy in the setting of increasing AKs would prevent clinical graft rejection.