We have examined the spontaneous and X-radiation-induced chromosomal damage in normal humans and in patients with retinoblastoma using the BudR-Giemsa technique in lymphocytes cultured for 48 h. 9 sporadic unilateral non-hereditary cases, 11 hereditary cases (8 bilateral sporadic and 3 unilateral hereditary cases) and 20 healthy individuals were studied simultaneously. No difference in the spontaneous frequency of chromatid and chromosome aberrations was observed between patients and controls. After treatment with 150 rad the frequency of chromosome exchange aberrations was higher in unilateral hereditary cases than the controls (42.0% +/- 5.3 and 22.3% +/- 2.6 respectively; p = 0.05). In bilateral sporadic retinoblastoma 2 different groups were observed. A hypersensitive group showed a significant increment in radiation-induced chromosomal exchange aberrations over the control group (46.2% +/- 5.4 and 24.2% +/- 2.1 respectively; p = 0.01). The other group had a chromosomal exchange frequency similar to normal individuals (26.5% +/- 2.0 and 24.2% +/- 0.4 respectively; p = 0.10). Sporadic unilateral non-hereditary retinoblastoma had an exchange chromosomal aberration frequency similar to control individuals (26.1% +/- 2.8 and 24.6% +/- 2.7 respectively; p greater than 0.10). These results suggest that: There is no relationship between spontaneous chromosome fragility and retinoblastoma. Sporadic unilateral non-hereditary retinoblastoma has normal chromosome sensitivity to X-irradiation. Some hereditary cases of retinoblastoma are sensitive to X-rays while others behave like normals. A mutation or a submicroscopic deletion at a DNA repair locus which is independent of the retinoblastoma gene may cause this radiosensitivity.