The depressed antibody responses resulting from the administration of live BCG i.v. to mice have been investigated. The antibody response of spleen cells to SRBC or DNP-Ficoll in vitro was followed using Marbrook culture vessels. Depressed responses were also found in vivo confirming the results obtained in vitro. The response in vitro of normal spleen cells was suppressed by the addition of spleen cells from mice injected with BCG but not by the medium in which they had been growing for 2 days. The response of the normal spleen cells was also not suppressed by freeze/thaw disrupted BCG spleen cells, suggesting that the depressed responses in the mice injected with BCG are due to an active suppression by intact cells. This was confirmed by the cell-depletion experiments. Removal of cells from the BCG-primed cell populations using carbonyl iron or adherence to plastic not only abrogated the depressed responses but revealed an underlying enhancement of the immune response. The data suggest that the suppressive cell might be a macrophage.