Guinea pigs of inbred strain 2 were vaccinated with BCG 1331 Copenhagen (K-Nr. 240-1) six to seven weeks before intradermal application of about 10(5) leukocytes from a highly leukemic animal in mixture with 10(7) colony forming units (CFU) of BCG. This presensitization with BCG totally abolished or strongly reduced the antitumor activity of L2C-cells adjoining BCG. Increase of bacterial mass applied from 1 X 10(7) to 2 X 10(8) CFU did not restore the antileukemic effect of BCG as observed in unvaccinated guinea pigs by a significant delay of death in a portion of animals and by the occurrence of long-term survivors. Since local reaction to BCG occurred much earlier in presensitized than in unvaccinated animals, we speculate that the destruction of tumor cells and hence the antigenic stimulus was too premature in presensitized animals to build up a BCG-mediated antitumor immunity.