Radiation-induced biochemical events that mediate the intracellular signal transduction leading to cell apoptosis are largely unknown. Limited evidence suggests the possible involvement of one or more protein-tyrosine kinases (PTKs) in radiation-induced cellular responses, including apoptosis. However, so far, a PTK(s) responsible for the radiation-induced tyrosine phosphorylation of cellular substrates has not been identified and the role of the PTK(s) in the radiation-induced apoptosis remains unclear. To examine the roles of Syk and Lyn in radiation-induced signal transduction and radiation-induced apoptosis, we analyzed Syk-deficient or Lyn-deficient DT40 B cells along with wild-type cells following radiation. When DT40 B cells were exposed to radiation, the activity of Syk kinase dramatically increased and reached a maximum with 0.25 Grays (Gy) (15 s), and then decreased, whereas Lyn kinase activity increased and reached a maximum with a dose of 1.00 Gy (1 min). However, an apparent difference was not observed in radiation-induced apoptosis among wild-type, Syk-deficient, and Lyn-deficient DT40 B cells. These results indicate that Syk and Lyn kinases are involved in radiation-induced signal transduction, with different kinetics. In addition, our results revealed that functional inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis. Thus, it is suggested that the activation of Syk or Lyn kinase alone may be sufficient to mediate the radiation-induced apoptosis in DT40 B cells, or both kinases may not be required for this biological process.