To investigate the occurrence and the prognostic significance of DNA aneuploidy in Hodgkin's disease, the nuclear DNA content of 70 patients with Hodgkin's disease was determined from paraffin-embedded tissue by flow cytometry. DNA aneuploidy was found in eight (11%) cases. None of the five lymphomas of the lymphocytic depletion type was aneuploid, and DNA aneuploidy was not associated with any of the histologic subtypes. DNA ploidy did not have significant association with prognosis, but the two patients with aneuploid lymphoma who died had the largest DNA indices measured (1.63 and 2.03). Patients with lymphoma with greater than 10% S phase cells had poorer crude survival rate (P = 0.01) and survival rate corrected for known intercurrent deaths (P = 0.002) than patients with lymphoma with less than 10% S phase cells. In multivariate analysis, age at diagnosis, sex, histologic subtype, and S phase fraction had independent prognostic value.