Sister chromatid exchange (SCE) analysis was carried out on peripheral blood lymphocytes of 20 familial malignant melanoma (FMM) and 39 sporadic malignant melanoma (SMM) untreated patients, belonging to 10 and 39 families, respectively. The study was extended to 39 unaffected close relatives of FMM patients, to 187 unaffected close relatives of SMM patients, and to 20 unaffected unrelated individuals (control group), all examined under the same conditions. The mean SCE rates/cell were significantly higher in MM families than in the control group, and in melanoma patients than in their close relatives. The mean SCE levels of FMM and SMM patients, (8.4 +/- 0.8 and 8.0 +/- 0.3, respectively) were similar, and so were the distributions of individuals in classes of increasing SCE values (with a modal value at 7-8 SCEs/cell). The mean SCE levels of close relatives of FMM and SMM patients were also similar (5.4 +/- 0.2 and 5.4 +/- 0.1, respectively, with a modal value at 4-5 SCEs/cell), and slightly higher than in the control group (4.7 +/- 0.2 SCEs/cell). More than 7 SCEs/cell were observed in the majority (41 of 59) of FMM or SMM patients, in a smaller fraction (25 of 227) unaffected relatives, and in none of 20 unrelated unaffected individuals. These observations favor the hypothesis that higher SCE levels may be an expression of constitutional lesions predisposing to this neoplastic disease.