The in vitro lymphocyte transformation test was compared to the skin test at intervals after aerogenic administration of bacille Calmette-Guerin vaccine to monkeys, and also at monthly intervals after aerogenic challenge of monkeys vaccinated and not vaccinated with virulent strain H37Rv of Mycobacterium tuberculosis. Individual responses varied, but several consistent patterns of sensitivity development could be discerned. The lymphocyte transformation test was more sensitive, and often positive when the skin test was negative, doubtful, or feeble. Conversion to tuberculin reactivity was detected by lymphocyte transformation in vitro earlier in the disease or after vaccination, and persisted longer after sensitivity to the skin test had waned or after the animals had become anergic by the skin test. Monkeys not vaccinated, but challenged, developed larger in vitro skin reactions and responses than animals that were either vaccinated and challenged or only vaccinated; however, the unvaccinated, challenged monkeys developed anergy to tuberculin and progressive disease more rapidly than other groups, and their cells became less responsive to phytohemagglutinin in vitro.