The conclusions from our studies to date may be summarized as follows. (1) Invasive E. coli strains causing neonatal meningitis are encapsulated. At least 80% of those strains inducing mengitis are K1 and approximately 40% of those strains isolated from infants with septicemia but without meningitis are also K1. Invasiveness is best related to the K1 antigen and not to E. coli O and H antigens. (2) The capsular content of CSF strains is not related to their invasiveness. In contrast to observations reporting higher K capsular polysaccharide content and molecular weight of E. coli invading the renal parenychma as compared with those E. coli confined to the bladder or in the stool, there were no differences among DSF K1 strains. Sepculation as to the mechanism of the invasive properties conferred by acidic capsular polysaccharides may be derived from the literature. Unencapsulated or "rough bacteria" are susceptible to the bactericidal action of agammaglobulinemice sera (15, 53). When injected into precolostral (agammaglobulinemic but complement containing), cesarian-delivered, and antigen-deprived piglets, unencapsulated bacteria are rapidly cleared from the circulation. In contrast, smooth bacteria injected into these same animals circulate without detectable splenic or hepatic clearance, multiply, and result in the death of these animals. The mechanism of the resistance of encapsulated bacteria has been postulated to be due to the inaccessibility of the deep somatic antigen structures capable of activating the alternate complement pathway system. Thus, opsoninization and other host complement-dependent activities may of necessity be antibody mediated for encapsulated bacteria. This complement resistance of encapsulated organisms may be quanititative and studies should be done to determine differences among various K1 E. coli strains. (3) K1 strains are widely prevalent among infants, children, and adults and are quickly transmitted to infants. In most cases the source of the infecting strain in diseased infants is the mother. However, transmission from attendants, demonstrable in our studies, is also a possible mechanism. (4) A protective role of serum anticapsular antibodies in animal models has been demonstrated. Our initial observations indicating low serum K1 antibodies in the general population and the finding that K1 antibodies are predominantly IgM in two animal species studied so far suggest that colostral K1 antibodies may be important in conferring immunity to this disease.