CA125 is an antigenic determinant recognized by monoclonal antibody CA125 raised against a serous ovarian cancer cell line. Elevation of this antigen has been reported in over 80% of women with epithelial ovarian cancer and many other diseases including both malignant and non-malignant ones. However, in non-Hodgkin's lymphoma (NHL) only a few reports have focused on this topic thus interesting us. In order to exploit its possible role in this field, a total of 61 eligible patients with a diagnosis of NHL were studied. Serum CA125 was measured by radioimmunoassay (RIA) prior to any operative procedures or chemotherapy. Serum CA125 above 35 U/ml was seen in 47.7% of nodal NHL (n = 44) and 70.6% of extranodal NHL (n = 17) with an overall positive rate at 54.1%. The elevation of serum CA125 correlates well with the presence of peritoneal involvement and therefore, with disease extent to some degree. No correlation between it and the histological type or with the B symptom was the rule. Avidin-biotin peroxidase stain by anti-CA125 MoAb was applied to identify the tissue content of this antigen in 15 cases of whom 11 had CA125 well above 35 U/ml. None of the 15 cases examined showed positive result. In conclusion, serum CA125 is probably no more than an indicator of peritoneal stimulation released by tumor invasion rather than a tumor product. The possible role in disease follow-up remains to be elucidated.