Optimal stimulatory doses of purified phenol-water extracted lipopolysaccharides (LPS) from 5 selected strains of 3 putative periodontopathogens (Fusobacterium nucleatum, Prevotella intermedia, and Veillonella), 3 strains of 2 nonoral bacterial species (Bacteroides fragilis and Salmonella enteritidis), and pokeweed mitogen (PWM) induced significantly higher maximum mitogenic responses and polyclonal Ig production in cultures of unfractionated spleen cells from nu/nu-BALB/c (nude) than from BALB/c (normal) mice. Compared with PWM, the LPS were stronger mitogens showing relative mitogenic capacities: B. fragilis LPS greater than F. nucleatum LPS greater than S. enteritidis LPS, Veillonella LPS, and P. intermedia LPS. B. fragilis LPS was the most and S. enteritidis LPS the least effective polyclonal B cell activator of total Ig, IgG2a, IgG2b, IgG3, IgA, and IgM secretion. IgG1 was not detected. P. intermedia LPS was the strongest IgA inducer. Kinetic observations indicated mitogenic responses and polyclonal B cell activation in a close sequential order in nude and normal cells. The LPS were potent Ag- and T cell-independent polyclonal B cell activators and LPS of subgingival plaque bacteria may therefore play a nonspecific role in the pathogenesis of periodontal diseases.