A pharmacologic study of clofazimine (B663) was carried out in mice and human subjects to provide information needed for interpretation of data from studies of drug action in the two species. The quantities of B663 in mouse carcasses were measured to determine the half-time of disappearance (t ½) of the drug and the absorption of the drug after oral administration. The antimicrobial activity of orally-administered B663 was studied in mice infected with Mycobacterium leprae and correlated with the quantity of B663 in the carcass. Published studies of the effect of the drug in murine infections with M. leprae and M. tuberculosis were reinterpreted. The t ½ of B663 is about 1 week in male BALB/c mice. The antimicrobial effect of the drug appears to require a concentration in the mouse carcass smaller than 1 mg/kg for M. leprae and greater than 5 to 10 mg/kg for M. tuberculosis. The concentration of B663 was also measured in the plasma, urine and feces of volunteers and leprosy patients. The t ½ of the drug is at least 70 days in man. The disposition of the drug thus differs greatly between the two species, making difficult the transfer of information from laboratory to clinic.