The immunomodulatory properties of several lipopolysaccharides (LPS) derived from clinical isolates of Pseudomonas aeruginosa, Branhamella catarrhalis, and Bordetella pertussis were evaluated for their capacity to influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III), which is known to be regulated in a negative and positive manner by suppressor and amplifier T cells (Ts and Ta, respectively). The administration of LPS, two days after immunization result in a significant increase in the antibody response. Such enhancement appears to be due to the ability of the lipid A moiety of LPS to abolish the negative effects of activated Ts, thereby enabling Ta function to be more fully expressed. By contrast, treatment with LPS a the time of immunization with SSS-III-specific i.e., prior to the activation of Ts induces significant suppression of the SSS-III-specific antibody response, such suppression is independent of the capacity of LPS to activate B cells polyclonally, an activity generally attributed to the lipid A fraction of LPS. Studies conducted with LPS of P. aeruginosa indicated that the suppression induced is T-cell dependent and mediated by the polysaccharide (PS) fraction of LPS: it appears to be due - at least in part - to the capacity of PS to expand or increase the size of the precursor pool of Ts, activated in response to SSS-III. These findings suggest that the capacity of the PS fraction of LPS to augment Ts function may play an important role in the pathogenesis of certain gram-negative infections.