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Acedapsone (DADDS), a repository sulfone given by injection five times a year, has been used since 1967 for the treatment of all leprosy patients in the Karimui, an area of difficult access. More than 460 patients have been treated, 336 beginning in November 1967 and continuing through the latest assessment 6 years later. The injections have been well received and they have been administered very regularly. Clinical observations were begun before 1967, so a base-line of assessments was available for the patients whose disease appeared before that time. The response to DADDS therapy has been satisfactory except in 5 of the 28 multibacillary patients in whose smears solid-staining Mycobacterium leprae have reappeared. M. leprae was isolated in mice from three of these patients; one strain has been proven to be completely susceptible to dapsone (DDS), and the other two very probably are. DDS levels in the plasma of these five patients were normal and well above the minimal inhibitory concentration. The most probable explanation is that a few viable M. leprae survived in the presence of inhibitory concentrations of DDS for the 4 to 6 years during which dead bacilli were disintegrating and disappearing from the tissues. The other 23 multibacillary patients responded satisfactorily. The decrease in the number of M. leprae in the skin smears has been most prompt in patients with low initial bacterial loads and in those with borderline lepromatous diagnoses. A high initial bacterial load and a fully lepromatous diagnosis were associated with a slow initial loss of M. leprae in the 1st year, followed by a more rapid loss the next year. All of the multibacillary patients have now been treated by the addition of a 90-day course of rifampicin.