To understand the mechanisms of adaptational changes in signal transduction involving tyrosine phosphorylation, studies have been made in animals subjected to whole body ionising radiation. Wistar rats (100-120g) were exposed once to X-rays at 0.5 Gy. After 12 h they were humanely killed. The levels of protein tyrosine phosphatase (PTP) activity were measured in spleen and thymus lymphocytes after incubation with ‘cell-linked protein A’, an immune stimulating factor possessing B- and T-cell blast-transforming activity. Exposure to radiation caused a decrease in the PTP activity stimulating action of mitogen incubation in the thymus, but not in the spleen (Table 1). The catalytic features of purified CD45, the major transmembrane PTP of the lymphocytes, were evaluated using paranitrophenylphosphate and phosphotyrosine as, respectively, non-specific and specific substrates. With the former, irradiation was shown to cause a decrease in V_max but an increase in affinity. With phosphotyrosine both V_max and affinity decreased (Table 2). These data suggest that exposure to radiation causes an increase in non-specific enzyme activity with a decrease in the ability to dephosphorylate the specific substrate. A study of cooperativity parameters shows that cooperativity between two phosphatase domains increased following radiation. Analysis of inhibitor kinetics showed that radiation caused a change from competitive to mixed inhibition.