Protein kinase C (PKC, now known as Prkc) plays an important role in the response of cells to radiation, but little is known about the specific response of each isozyme in the radiation-induced response of cells in whole animals. However, most studies are based on single cells. There is a paucity of data on signaling after whole-body irradiation. In this study, a comparison has been made between the expression of Prkc isozymes after in vivo and ex vivo irradiation. There was a significant difference in the dose response of the isozymes. In animals in which lymphocytes were irradiated ex vivo, the expression of the Prkca isozyme was found to be maximum at 3 Gy, while in vivo irradiation did not increase the expression beyond that of 1 Gy. Prkcd was marginally activated after 0.1 Gy ex vivo irradiation, whereas there was significant activation of expression after in vivo irradiation with 3 Gy. The response of Prkcz was found to be similar to that of Prkcd. Prkc is a crucial enzyme that is being used to manipulate the response of tumors to radiotherapy. Conventional radiotherapy is delivered at low doses, and hence only those isozymes that are activated at these doses should be taken into consideration. Moreover, the differences between the response of a single cell and that of the whole animal must be considered.