Soluble and cell surface antigen-induced triggering of highly purified human T and B cells was studied measuring 3H-thymidine incorporation in vitro. T cells but not B cells from antigen-sensitive donors responded to specific soluble antigen challenge. Nonsensitized cells failed to respond. The addition of sensitized T cells to autologous B cells did not induce B cells to proliferate in response to soluble antigen. In one-way mixed leukocyte cultures, T cells but not B cells incorporated 3H-thymidine in response in allogeneic mitomycin-treated targets. In contrast, both T and B target cells were capable of inducing proliferation of allogeneic T cells.