Monoclonal antibody SP-2, which binds to a 90,000 daltons tumor-associated antigen termed 90K, was generated by mouse immunization with proteins released by human breast cancer cells into the culture medium (Iacobelli et al: Cancer Res 46: 3005-3010, 1986). Elevated 90K levels have been previously reported in the serum of patients with various malignancies. We investigated whether the circulating levels of 90K antigen might be related to prognosis of patients with Non-Hodgkin's Lymphomas (NHL). Serum samples were obtained from 50 apparently healthy blood donors and 81 patients with NHL. Circulating serum 90K concentrations (U/ml) were determined by a solid-phase immunoradiometric assay (IRMA) by a two-step procedure. Serum 90K levels were significantly higher in patients with NHL than in healthy controls (p=0.004). The Kaplan-Meier analysis of overall survival showed that patients with 90K-negative (serum 90K levels less than or equal to 16 U/ml) survived longer than patients with 90K-positive sera (less than or equal to 16 U/ml) (p=0.004). Multivariate regression analysis revealed that serum levels of LDH and 90K were the two independent prognostic variables for predicting overall survival. We propose that an elevated 90K antigen level in sera is a predictor of poor prognosis in NHL.