The neuroradiological manifestations of bilateral single-session gamma (gamma)-irradiation to normal tissue contained in the internal capsule after gamma knife capsulotomy for otherwise intractable anxiety disorders were studied. In nine consecutive patients, a target maximum dose of 200 Gy was administered in a target volume of 276 +/- 42 mm3 (mean +/- SD) within the 50% isodose level. Serial computed tomographic and magnetic resonance imaging scans were undertaken from 3 to 44 months after irradiation. After surgery, a necrotic lesion appeared on computed tomographic scans, reaching its maximum volume (900 +/- 800 mm3) at 6 to 9 months, then decreasing (to 457 +/- 400 mm3) over the first postoperative year. This volume correlated with the mean isodose level of 91 (range, 41-143) Gy. On T2-weighted magnetic resonance imaging scans, the reaction tissue volumes were considerably larger and took longer to disappear than expected. In 15 targets, maximum reaction volumes were recorded at 1 to (approximately) 2 years after irradiation. In the remaining seven targets, smaller reaction volumes were observed, with no clear maxima appearing during 3 years of observation. In a pilot case, a lower target maximum dose of 160 Gy and a radiation volume of 275 mm3 within the 50% isodose gave only minimal surrounding tissue reactions. This report serves to alert clinicians that the tissue reaction volumes and the time course of their development after high irradiation doses may be less predictable than expected from previous observations in smaller radiation volumes. For this reason, lower irradiation doses and smaller volumes should be used in the future, and the time factor should be taken into account when interpreting computed tomographic and magnetic resonance images of gamma-knife-induced lesions.