To evaluate the role of serum CA 125 levels for the diagnosis, follow-up, and prognosis in childhood non-Hodgkin's lymphomas (NHL), 44 children (35 newly diagnosed patients and 9 patients with relapsed or progressive disease, median age 6.5 years, M/F ratio 2.1) with NHL were included in this study. CA 125 levels in serum and/or ascites and effusions were measured by radioimmunoassay. The upper limit of normal was 35 IU/mL. The correlation of CA 125 levels with tumoral location and treatment results were investigated. A total of 27 (61.4%) patients had increased and 17 patients had normal serum CA 125 levels. Fifteen patients with increased CA 125 levels had malignant ascites, pleural effusion, or both, although none with normal CA 125 levels had any serous membrane involvement. The mean CA 125 levels were 72.5 IU/mL in patients with no serosal involvement (ascites or effusion) and, 144.0, 273.7, 324.3 IU/mL in patients with pleural effusion, ascites, and ascites + effusion, respectively. The mean CA 125 levels in ascites and pleural effusion were 202.1 and 156.2 IU/mL, respectively, and were similar to the corresponding serum levels. The increased CA 125 levels returned to normal in 18 patients whose diseases were in remission during the follow-up. One-year survival rate for newly diagnosed patients was 80.2 and 87.5% in patients with increased and normal serum CA 125 levels, respectively. In conclusion, CA 125 levels were significantly higher in patients with serous membrane involvement and there was a correlation between treatment response and marker levels. Little is known about the expression of CA 125 in NHLs. This is the first report suggesting that serum CA 125 levels can be a useful marker for the follow-up of childhood NHL. CA 125 seems to be a promising tumor marker in the assessment of prognosis and therapeutic response in non-Hodgkin's lymphomas.