The roles of capsule, pili and Class 5 outer-membrane proteins (Opa and Opc) of Neisseria meningitidis (Nm) in bacterial interactions with human monocytes were investigated using several meningococcal isolates of different serogroups. The presence of either Class I or Class II pili in capsulate strains of several serogroups had no significant effect on adherence to and internalisation by monocytes. Using clonal variants derived from a non-piliated serogroup A strain, C751, it was observed that capsulate bacteria (cap+) failed to interact with human monocytes in significant numbers whether or not they expressed outer-membrane proteins. These bacteria were also resistant to phagocytic killing. For capsule-deficient bacteria, expression of the Opc protein or OpaBC751 correlated with high levels of association, while the expression of OpaDC751 or OpaAC751 resulted in comparatively lower levels. Bacteria expressing undetectable levels of Opc or Opa proteins (Opc-, Opa-) failed to interact with monocytes. In phagocytic killing assays, Opc-expressing bacteria (Opc+) as well as Opa-expressing bacteria (Opa+) were killed more readily than Opc-, Opa- bacteria (30% decrease in viability of Opc+ bacteria; 18%, 10% and 8% decrease in viability of OpaB+, OpaD+ and OpaA+ bacteria). A study of intracellular survival showed a gradual decrease in viability of both capsulate and capsule-deficient bacteria. However, proportionately greater numbers of capsule-deficient bacteria were internalized and consequently larger numbers survived over a 4-h period. Prolonged bacterial survival within phagocytic cells may have implications in dissemination of bacteria by carriage within these cells.