The study demonstrates that the sensitivity of endothelial cells to irradiation in vitro is significantly affected by the microenvironmental conditions under which the experiment is carried out. When irradiated plateau phase bovine aortic endothelial cells were assayed for colony formation on top of uncoated plastic of standard culture dishes, the dose survival curves showed Do values of [mean (S.D.)] 107 (6) cGy and Dq of 63 (28) cGy (calculated according to the single-hit multitarget model). When assayed in dishes precoated with the autologous natural basement membrane-like extracellular matrix (BAEC/ECM) the curves showed a similar Do [106 (2) cGy], but the Dq was 194 (8) cGy (P less than 0.05), indicating that components of natural ECM confer in endothelial cells an improved capacity to repair radiation lesions and to restore the clonogenic capacity. However, when the natural but biologically unrelated HR9-bFGF/ECM was used, a decreased repair capacity was noted with Dq of 156 (30) cGy (P less than 0.05 compared with BAEC/ECM). The data demonstrate the high specificity of the repair function to interactions with autologous matrix components, and emphasise the need to select relevant experimental conditions when parameters of the radiation response in vitro are used to predict the response in vivo.