Pharmacokinetic studies of rifampin were performed in 38 infants and children after administration of three different oral formulations. Mean peak serum concentrations of from 9 to 11.5 microgram/ml were observed one hour after a 10-mg/kg dose and the average half-life was 2.9 hours. Patients who received rifampin suspension in applesauce had smaller serum concentrations and area-under-the-curve values than did those who were given suspension alone. The mixture of rifampin powder and applesauce resulted in more variable serum levels. The concentrations of drug in tears from 18 subjects were similar to those in serum. All but one of 118 saliva specimens obtained from two to eight hours after the 10-mg/kg dose had antimicrobial activity. Of samples taken at two hours, 95% contained rifampin levels that exceeded the minimal bacterial concentration for 15 Haemophilus influenzae type b strains. Bactericidal activity against Haemophilus correlated with salivary rifampin concentrations and was detectable in virtually all specimens containing greater than or equal to 0.8 microgram/ml. These data provide the pharmacokinetic basis for rifampin prophylaxis of close contacts of H influenza type b disease, but are insufficient alone to recommend routine usage of rifampin for this purpose until results of additional epidemiologic studies are available.