Antibody responses to Pneumococcal Polysaccharide type 3 (PnAb) are independent of T Cells in the murine model. To confirm the putative T cell independent nature of the response in humans, we studied PnAb secretion by in vitro lymphoctye cultures. Twelve day culture supernatants of blood mononuclear cells drawn before and 1 and 3 weeks post-immunization with Pneumococcal Vaccine were assayed for total IgG and PnAb by ELISA. Maximum PnAb secretion occurred at 1 week post-immunization in both unstimulated (177 ± 90 ng/ml) and pokeweed stimulated (300 ± 200 ng/ml) cultures. PnAb secretion was not due to polyclonal stimulation since no change in anti-tetanus toxoid secretion was found and a paradoxical decrease in total IgG secretion occurred (pre=2.4 mcg, 1 wk post = 1.3 mcg, p < .001). Addition of purified pneumococcal type 3 antigen (.001-10 ng/ml) had no effect on PnAb secretion. B cell enriched T cell depleted cultures had similar PnAb kinetics to unfractionated mononuclear cells: pre = 1.5 ± 1.6 ngAb/mcgIgG, 1 wk post = 180 ± 175 ngAB/mcgIgG, 3 wk post = 381 ± 380 ngAb/mcgIgG. Addition of T cells ± pokeweed mitogen, purified IL-2, or allogeneic T helper factor from mixed lymphocyte culture supernatant had no effect on PnAb secretion expressed per mcg total IgG. These studies suggest that Pneumococcal Polysaccharide type 3 is a T cell independent antigen in humans which may activate B cells in a manner distinct from conventional protein antigens.