The pathogenesis of ankylosing spondylitis (AS) remains unknown, although previous studies have strongly suggested that it may result from immunological aberration. To further explore the pathogenetic mechanisms, in vitro syntheses of immunoglobulins and interleukin-2 (IL-2) by peripheral blood mononuclear cells (MNC), and the serum level of the interleukin-2 receptor (IL-2R) were studied in 35 patients with definite AS and in 28 healthy controls. MNC were cultivated in the presence of pokeweed mitogen (PWM) for seven days. Immunoglobulins in the supernatants were measured by rate nephelometer (Immunochemistry System Analyser II, Beckman.) In vitro synthesis of IL-2 was carried out by cultivating MNC in medium only; in medium containing physiological concentration of the male sex hormone i.e., testosterone 500 ng/dl and estradiol 2 ng/dl; and in medium containing physiological concentration of female sex hormone, i.e., testosterone 50 ng/dl and estradiol 20 ng/dl. IL-2 was quantitated using an IL-2-dependent cytotoxic T lymphoid cell line (CTLL). Serum IL-2R was measured using an IL-2R test kit (CELLFREE, T Cell Sciences, Cambridge, MA). The results showed: In vitro synthesis of IgG, IgA and IgM was significantly higher in AS than in controls; In vitro synthesis of IL-2 was significantly enhanced by testosterone in normal control, but not in AS; and Serum IL-2R was significantly elevated in patients with AS. These findings, viewed in conjunction with previous results here, lead to postulation that an inflammatory process, elicited in HLA-B27-positive males and caused by an infectious agent invading via the mucosa may both cause immunological abnormalities and provoke various symptoms and signs of AS.