Rationale: R207910 (TMC207 or J) is a member of the diarylquinolines, a new family of antituberculous drugs with high bactericidal activity when given daily in the murine model of tuberculosis. R207910 exhibits a long half-life and thus is a good candidate for once-weekly therapy of tuberculosis. Objectives: To study the activity of once-weekly R207910 monotherapy and combinations of R207910 with other antituberculous agents (isoniazid, rifapentine, moxifloxacin, and pyrazinamide). Methods: The established infection model of murine tuberculosis was used. Colony counts were determined in the lungs. Measurements and Main Results: Eight weeks of monotherapy reduced the bacillary load by 3 to 4 log10 for rifapentine and by 5 to 6 log10 for R207910 (P