The nuclear DNA content was microspectrophotometrically measured in 16 resected esophagi having dysplasia, carcinoma in situ and/or early invasive squamous carcinoma. First, the epithelial thickness in (1) normal squamous esophageal epithelium and (2) dysplasia-carcinoma in situ areas was divided into three equal compartments (i.e., basal-parabasal, intermediate and superficial) in five cases. In the normal epithelium, while some of the nuclei in basal-parabasal normal squamous cells had elevated DNA values (corresponding to the natural DNA replication in these cells), intermediate and superficial (nonreplicating) normal squamous cells showed a more definite clustering about the 2c value. In the nonnormal epithelium, the percentage of cells with DNA levels exceeding the normal tetraploid value was highest for the intermediate zone. Therefore, in all 16 cases, normal intermediate cells were measured as internal controls, against which the DNA levels of cells in the intermediate compartment in the areas of dysplasia and/or carcinoma in situ were compared. In areas of dysplasia, two different DNA patterns were observed: one clustering around the normal diploid region and the other with aneuploid values. While the former corresponded to some of the lesions considered by conventional histologic examination to be slight and moderate dysplasias, the aneuploid pattern corresponded to the remaining slight and moderate dysplasias as well as to the severe dysplasias. The possibility that "diploid dysplasias" are reactive (i.e., nonneoplastic) lesions due to chronic inflammation or are "dormant" nonprogressive dysplasias, while aneuploid dysplasias are more aggressive lesions, seems to be substantiated by the fact that all areas with carcinoma in situ or with microinvasive squamous carcinoma had aneuploid nuclei.