The overall objective of this propoal is to delineate microbiologic, immunologic and genetic factors which may contribute to the extraordinary incidence of invasive Hemophilus influenzae type b (Hib) disease in Eskimo infants. To evaluate the extent and character of exposure, we will determine in a prospective study of high risk villages the rates of Hib acquisition and carriage in young Eskimos and their family members. By analysis of outer membrane proteins (OMP), we will characterize differences between Hib strains recovered from carriers and from Eskimo children with invasive disease. Furthermore, we will delineate differences in OMP composition of disease causing strains recovered from population groups with markedly different disease risk (Eskimos, Indians, non-native Alaskans and U.S. controls). We will characterize the natural acquistion of Hib anticapsular antibody in this population and determine the immunoglobulin class specific content (ELISA) and the relationship of IgG subclass levels. To assess the possible contribution that cross reacting bacteria may make to anticapsular antibody levels, we will culture children prospectively for cross reacting bacteria as part of the study of Hib acquisition and carriage, and we will evaluate sera with Hib anticapsular antibody (RIA) for the proportion of antibody inhibited by purified poly saccharide of E. coli K100. We will measure anticapsular antibody in breast milk of Eskimo women and in controls and also determine epidemiologically the possible protective influence of breast feeding. To assess the possible association of genetic factors with Hib disease risk, we will determine HLA allotypes (A.B.C.DR) and immunoglobulin allotypes in this population as part of a family study and a matched case-control population study.