On the basis of a retrospective study of 327 patients with Hodgkin's disease (HD), the prognostic significance of several factors, accepted previously and recently proposed, has been analyzed with regard to response to treatment and the survival time. Multivariate regression analysis strongly decreased the number of potentially prognostic parameters. The only independent, pretreatment factors negatively influenced by either time of survival or response to treatment were the following: age at diagnosis of more than 45 years, advanced (IIIB/IV) clinical stage, poor clinical status according to Karnofsky's scale (score less than 70), presence of systemic symptoms, mixed cellularity/lymphocyte depletion histological type, multisite peripheral nodal localization of the disease, abdominal lymphadenopathy, and large primary tumor mass (bulky disease). Short time to achieve complete remission (during the first four courses of chemotherapy) has proven to be significantly positive predictive factor. Cumulative dose of cytostatics lower than programmed was a significantly negative prognostic factor that correlated with a shorter time of survival. Lack of or a too-low dose of radiotherapy had the same predictive value. High activity of serum lactate dehydrogenase correlated moderately with poor response to the first-line treatment but did not influence the survival time. Other clinical, morphological, and biochemical parameters influenced neither the prognosis nor the response to treatment. Additionally, immunohistochemical examinations for proliferating cell nuclear antigen and the protein products of the p53 and bcl-2 genes were performed on the lymph nodes obtained from the patients with HD. High expression of proliferating cell nuclear antigen, p53, and BCL-2 correlated with poor response to the treatment and/or short time of survival. Statistical analysis has led us to the conclusion that the pretreatment expression of these oncoproteins can be taken into consideration as a new prognostic factor in HD.