To explore the hypothesis that low-dose immunization might induce preferential Th1 cell immunity, 76 adults were vaccinated with one of four doses of bacille Calmette-Guérin (BCG): The doses contained very low (1.6 x 10(5) cfu), low (3.2 x 10(6) cfu), standard (1.6 x 10(8) cfu), or high (3.2 x 10(8) cfu) levels of BCG. Delayed-type hypersensitivity responses occurred 8 weeks after vaccination in 10% of persons given very low or low doses of BCG, compared with 95% and 100% of persons given standard or high doses, respectively. Lymphoproliferative responses, which were increased only for high-dose vaccinees, peaked 2 weeks after vaccination and were directed chiefly against Mycobacterium tuberculosis-secreted proteins, particularly the antigen 85 complex. Significant increases in mycobacteria-specific interferon-gamma expression were present 16 weeks after vaccination only for persons given standard or high doses of BCG. Percutaneous BCG appears capable of inducing a temporary Th1-like immune response, but standard or higher dosages are required.