Microwave coagulation therapy (MCT) has been applied to small hepatic carcinomas. To clarify the sequential changes in histology and the viability of the microwave-irradiated tissue, we examined irradiated normal rat liver with enzyme histochemistry for acid phosphatase (AcP). In the samples immediately after irradiation, the margin of the irradiated region was indistinct in H&E stain, while AcP enzyme histochemistry disclosed well-demarcated distinct zones: an inner zone adjacent to the electrode without AcP activity and a surrounding outer zone with attenuated enzyme activity. In the inner zone, the nuclear staining with hematoxylin persisted for at least one month, whereas that in the outer zone disappeared 24 hr after irradiation and was accompanied by neutrophilic infiltration and then replaced by granulation tissue. Our results indicated that microwave irradiation caused tissue fixation in the inner zone and coagulative necrosis in the outer zone. Because microwave-fixed cells retained their morphology well, they appeared very similar to normal cells in H&E-stained section. Enzyme histochemistry may be useful for assessment of cellular viability after microwave irradiation, by enabling us to distinguish fixed cells from viable cells.