The main initial and evolutive variables of 133 patients with large-cell lymphoma treated with adriamycin-containing regimens were evaluated for prognostic significance. At the time of analysis, 66 patients had died with the median survival of the series being 48.9 months. Variables associated with poor prognosis in the univariate study were: lymphoma of immunoblastic subtype, advanced Ann Arbor stage, presence of B-symptoms, poor performance status, bulky disease (≥10cm), involvement of two or more extranodal sites, bone marrow infiltration, and high serum LDH levels. In the multivariate analysis, Ann Arbor stage (p<0.001), bulky disease (p= 0.004), performance status (p= 0.018), and histologic subtype (p= 0.021) retained their prognostic value. After excluding those patients with localized disease (stage I), the Ann Arbor staging system lost prognostic significance in favor of bone marrow infiltration (p= 0.009) and serum LDH (p<0.001). However, when response to treatment was included in the regression model, it proved to be the most important prognostic factor (p<0.001), followed by serum LDH (p= 0.004). On the other hand, when the analysis was restricted to complete responders, serum LDH at diagnosis was the only parameter useful to predict survival (p= 0.008). Finally, five recently proposed prognostic classifications were useful to separate different risk-groups of patients when applied to the series.