The safety and immunogenicity of the HbOC conjugate vaccine have been evaluated in a study population of 61,080 children in the Kaiser Permanente Medical Care Program of Northern California. Half of the population served as controls. The vaccine was given as part of a three-dose regimen in the first year of life with the first dose given between 6 weeks and 6 months of age, a minimum interval of 1 month between doses and with the third dose given by 1 year of age. The vaccine was highly immunogenic with 97% of infants developing 1 microgram/ml or more of anti-polyribosyl phosphate antibody as measured by Farr assay 1 month after completion of the three-dose series and with 71% maintaining this concentration until a booster dose was given at approximately 18 months of age. There were three cases of Haemophilus influenzae type b disease after the first dose of vaccine and two of these children died. However, there was no statistically significant difference between either the incidence of H. influenzae type b disease or the mortality rate in infants after one dose of HbOC vaccine when compared with H. influenzae type b disease incidence and mortality in unvaccinated children of the same age. The rate of sudden infant death syndrome following HbOC vaccine was lower than that observed within the Kaiser Permanente Medical Care Program as a whole or in the three counties in which sudden infant death syndrome surveillance was tabulated. Immediate local and systemic reactions were evaluated by telephone interviews of 6887 infants within 72 hours of vaccine.(ABSTRACT TRUNCATED AT 250 WORDS).