We investigated the induction and disappearance of DNA lesions that are detected as single-strand breaks (SSBs) with the alkaline filter elution technique, in human peripheral blood lymphocytes (PBLs) following exposure to N-ethyl-Nnitrosourea (ENU). In PBLs of the 15 individuals studied, 35 ± 16% (mean ± SD) of the SSBs present at the end of a 20 min treatment disappeared within 1 h; up to 24 h posttreatment no further disappearance was observed. Inter individual differences in SSB disappearance were considerable; in two cases, almost no SSBs disappeared over the 1 h period. In PBLs of the same 15 individuals 85 ± 3% (mean ± SD) of the SSBs induced by 4 Gy of γ-rays were found to disappear within 1 h, which indicated no interindividual differences. Multiple blood sampling at 1 month intervals indicated that interindividual differences in ENU-induced SSB repair are constant and do not vary with time. The low rate of SSB disappearance appeared to correlate with low cell survival after ENU exposure, measured as a reduction in phytohemagglutinin-stimulated incorporation of [3H]- thymidine. The cytosine analog 1-β-D-arabinofuranosylcytosine completely inhibited SSB disappearance, indicating that the removal of the repairable ENU-induced SSBs involves excision repair events.