From 1982 to 1986, nine patients with non-Hodgkin's lymphoma primarily involving the pancreas were managed at the Johns Hopkins Medical Institutions. This group of nine patients represents 2.2% of patients with non-Hodgkin's lymphoma (nine of 402) and 4.9% of all patients presenting with pancreatic malignancies (nine of 182) at the Johns Hopkins Medical Institutions during this period. Computed tomography (CT) scan findings of a large pancreatic mass (6 cm) with extrapancreatic extension and significant retroperitoneal lymph node enlargement suggested lymphoma. Diagnosis was established by radiographically-guided needle biopsy in four patients, by laparotomy in four, and by peripheral lymph node biopsy in one. In five jaundiced patients, initial chemotherapy with the nonhepatotoxic agents cyclophosphamide and prednisone resulted in marked tumor regression, allowing for early resolution of jaundice and subsequent addition of more aggressive adriamycin containing combination chemotherapy. Overall, complete remission has occurred in six of nine patients, with a median survival of 24 months (range 4-69 months). It is concluded from this experience that the majority of patients with pancreatic lymphoma can be managed without surgery. Excellent control of symptoms, including jaundice, as well as long-term remission, can be obtained with chemotherapy alone. The only role for surgery in this setting may be to aid in establishing the diagnosis when percutaneous biopsy is nondiagnostic.