Group B streptococci (Streptococcus agalactiae) of various serotypes (Ib/c, III/x, III/R, and B variant) and different sources of isolation were analyzed for their to interact with human mononuclear cells (MNC). Type I streptococci were obtained from a neonate dead of an invasive group B streptococcal infection. Examining the attachment of these bacteria to human peripheral lymphocytes and their ability to influence the proliferation of cultured adult and neonatal MNC, the following results were obtained: (1) Type Ib/c, III/x, and B variant strains adhered spontaneously to neonatal cord blood lymphocytes. The bacteria were bound by large lymphoid cells not detectable in the peripheral blood of adults. (2) Addition of group B streptococci to neonatal MNC cultures increased lymphocyte proliferation approximately 8 fold (n = 32) above the background. The reactivity of neonatal lymphocytes was highly reproducible with a mean peak proliferation close to day 5 of culture and a ratio of 60 CFU MNC. The control cell proliferation induced by Pokeweed mitogen (2 micrograms/ml) gave a mean stimulation index of 58. In contrast to cord blood cells, adult MNC responded only slightly with either proliferation of streptococcal binding. Clinical type I strain induced mean peak [3H]thymidine incorporation into neonatal MNC was approximately 16 times higher than into that of adults. Streptococcal adherence and lymphocyte activation did not depend on serotype specificity and clinical origin of the strains investigated. Therefore, the ability to interact with human cord blood lymphocytes seems to be a common property of group B streptococci.