DNA from 24 ovarian tumors, including 16 carcinomas, was examined for amplification of the proto-oncogenes c-myc, int-2, and rc-erbB-2. All cases of carcinoma were also examined by flow cytometry for DNA ploidy and cell cycle analysis, and eight cases of carcinoma were examined for estrogen and progesterone receptors. Protooncogene amplification was not detected in the DNA of benign ovarian neoplasms, or of ovarian carcinomas with low malignant potential. Amplification of c-myc was detected in six of 12 cases of invasive carcinoma, int-2 amplification was present in one case, and c-erbB-2 amplification was not detected in any case. Among the seven cases evidencing protooncogene amplification, three cases showed aneuploidy in tumor DNA, while four showed diploidy. Two cases which showed aneuploidy in tumor DNA did not demonstrate any degree of protooncogene amplification. Protooncogene amplification was frequently associated with morphologic nuclear anaplasia and high mitotic count. Six of the seven cases demonstrating c-myc or int-2 were of the serous type or showed some degree of serous differentiation, while none of the four cases of purely mucinous carcinoma had evidence of amplification. While the total number of cases in the study was limited, it would appear from the trend demonstrated by the data that protooncogene amplification (particularly c-myc) may be involved in the pathogenesis of aggressive common epithelial tumors of the ovary.