Nuclei with abnormal (aneuploid) DNA content were detected by flow cytometric analysis in 4 of 39 congenital melanocytic nevi and in 0 of 62 acquired nevi. Three of the 4 nevi with DNA-aneuploidy were greater than 20 cm in their largest diameter. We suggest that DNA aneuploidy is an indicator of a premalignant condition in congenital nevi in cases where histologic examination does not reveal any evidence for malignant melanoma. Cells with abnormal DNA content (aneuploid cells) are not uniformly distributed in giant congenital nevi: in one lesion we observed an area with a high percentage of cells with DNA aneuploidy, areas with a low percentage of aneuploid cells, and parts that were found to be normal by flow cytometric analysis. Nuclear pleomorphism was found histologically in the area with the high percentage of aneuploid cells while the areas with the low percentage of aneuploid cells were histologically normal. Thus, flow cytometry seems to be an additional sensitive method for the detection of nuclear abnormalities that are not always apparent by conventional histology. Increase in the relative amount of growth phase (S-phase cells), indicating elevated proliferative activity, was detected in 6 of 39 congenital pigmented nevi and in 6 of 62 acquired nevi.