Surface immunoglobulin (sIg) light chain analysis of peripheral blood lymphocytes (PBL) from 63 patients with non-Hodgkin's lymphoma (NHL) was performed to determine the ratio of kappa-bearing lymphocytes to lambda-bearing lymphocytes (kappa/lambda ratio). In 43% an abnormal kappa/lambda ratio was detected, implying the presence of a malignant clone in the peripheral blood (clonal excess). In 67% of cases with an abnormal kappa/lambda ratio, the absolute lymphocyte count was within normal limits and 20% did not have morphologic bone marrow involvement. Light chain analysis of bone marrow aspirates was performed in three of four patients with a circulating clone and normal bone marrow morphology. All three patients had abnormal bone marrow aspirate kappa/lambda ratios. The presence of a circulating clone was associated with morphologic bone marrow involvement (P less than 0.05). Nine patients with documented B-cell NHL were followed with repeated examinations. The presence of a circulating clone persisted in two patients refractory to therapy and in two patients otherwise believed to be in remission. Conversion to an abnormal kappa/lambda ratio occurred in two patients coincident with the development of new bone marrow involvement and in a third patient prior to the onset of frank leukemia. In three instances, the PBL light chain analyses remained within normal limits in patients with stable lymphadenopathy. The kappa/lambda ratio returned to normal in one patient responding to treatment with a partial remission, and remained within normal limits despite progression of lymphadenopathy in one patient, and local disease recurrence in another patient. These findings suggest that the detection of a circulating clone by sIg light chain analysis may be useful as a noninvasive approach to identify disseminated disease activity unsuspected on the basis of morphologic evaluations, but may not reflect the presence, progression, or recurrence of localized tissue lesions.