The origin of sporadic multinodular goiter is still uncertain. To obtain information on a number of unexplored immunological features, the distribution and characterization of T, B, and natural killer lymphocyte subsets were studied in the peripheral blood of 15 patients with multinodular goiter; 8 patients with Graves' disease (for reference purposes with a well-characterized autoimmune disease) and 29 age- and sex-matched healthy controls, combining double-staining immunofluorescence technique with monoclonal antibodies and flow cytometry. Although in both thyroid diseases increased CD3+ HLA-DR+ activated T cells (P < 0.01) were detected, in Graves' disease this was associated with decreased numbers of CD8 cells (P < 0.05) and an increased CD4/CD8 ratio (P < 0.01). These abnormalities were absent in multinodular goiter, which displayed increased CD8+ CD57+ cytotoxic/suppressor cells (P < 0.01). There was an increase in the percentage of natural killer cells expressing CD16 and CD57 antigens in multinodular goiter but not in Graves' disease. The B-cell associated antigens CD19 and CD19+ CD5+ were significantly increased in Graves' disease (P < 0.01), while the multinodular goiter patients exhibited only an increased number of B cells coexpressing the CD5 antigen (CD19+ CD5+), which was unrelated to the titers of anti-microsomal and antithyroglobulin autoantibodies. Our results point to the presence of several abnormalities of peripheral T, B, and natural killer lymphocytes in sporadic multinodular goiter, with a distribution pattern quite different from that observed in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)