Renal function was prospectively analysed in 26 patients treated with radiotherapy for various types of malignancies. In patients with gastric non-Hodgkin's lymphoma stage I-II (gNHL, n = 5), the 99mTc-diethylene-triamine-penta-acetic acid (99mTc-DTPA) renal uptake and the relative 99mTc-dimercapto-succinyl acid (99mTc-DMSA) accumulation decreased gradually and concomitantly in the high-dose, whole-volume irradiated left kidney (40 Gy/5, 5 weeks), down to 25 +/- 10% (mean +/- 1 S.E.M.) and 31 +/- 11%, respectively, after 6-9 years. The absolute 99mTc-DMSA uptake in the left kidney declined down to 33 +/- 12% whereas in the low-dose, whole-volume irradiated right kidney (12-13 Gy/3 weeks) it increased up to 187 +/- 11%. When considering renal volume changes with single photon emission computed tomography, the left kidney in the gNHL patients was reduced to 30 +/- 13%, with, surprisingly, a contralateral enlargement up to only 119 +/- 7% (P < 0.05). The overall renal function in this group of patients, as assessed by creatinine clearance and by [125I]iothalamate/[131I]hippuran clearance was reduced to 48-68%. In the Hodgkin's disease patients (HD, n = 7) given 40 Gy in 4 weeks to 30-50% of the left kidney, the 99mTc-DTPA filtration and the relative 99mTc-DMSA uptake in the left kidney was reduced to 75 +/- 4% and 81 +/- 3%, respectively. The absolute 99mTc-DMSA changes were 78 +/- 10% and 135 +/- 13%, respectively. No significant renal functional alterations were observed in patients with either ovarian carcinoma (n = 7) or seminoma (n = 7). These data suggest a significant, compensatory response of the non-irradiated or low-dose irradiated kidney which, however, appears to be incomplete after contralateral, whole-volume, high-dose irradiation. Such compensatory response might be overestimated when considering only relative or absolute changes in radioactivity uptake.