We conducted a multicenter trial designed to assess the efficacy of three different drug regimens on eradication of Haemophilus influenzae type b (HIB) from the nasopharynx of household contacts of patients with invasive type b Haemophilus disease. The drug regimens studied were rifampin, 20 mg/kg, once daily for four days; rifampin, 10 mg/kg, twice a day for four days; and placebo, once daily for four days. Shortly after admission of the index patient to the hospital, 26% of 492 household contacts were found to be colonized with HIB. Both rifampin regimens eradicated carriage significantly better than placebo at 10 and 30 days (P = .001). However, among contacts whose cultures were initially negative, new acquisition of the organism occurred infrequently in this 30-day follow-up period regardless of the drug or placebo regimen prescribed. We also measured the concentration of anticapsular antibody in sera obtained from contacts younger than 6 years of age. Samples were obtained soon after admission of the index patient to the hospital and 30 days later. Several carriers younger than 2 years of age had low concentrations of antibody in both specimens. In contrast, nearly all carriers 2 to 5 years of age had high concentrations of antibody even in the first sample. Children who were not carriers usually had low antibody concentrations which did not increase during the period of observation. Our results suggest that most intrafamilial spread of HIB occurs prior to hospitalization of the index patient and stimulates immunity in contacts older than 2 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)