Activation of phospholipase C-γ isozymes has recently been shown to involve their translocation to the participate fraction in the rat basophilic leukemia cell line following aggregation of the high affinity receptor for IgE. We now report that a similar process can be observed in human B and T lymphocytic tumor lines following stimulation with anti-TCR and BCR antibodies. In both the B and T cell lines, PLC-γ1 rose more than five-fold in the participate fraction following aggregation of the antigen receptor. PLC-γ2 was not detected in T cells; in the B cells, it was present in relatively high amounts in the participate fraction from unstimulated cells, and only a small further rise was noted after activation. After stimulation of the BCR or TCR in the respective ceil lines, the 24 kD adapter protein GRB2 and similar sets of tyrosine phosphoproteins co-precipitated with PLC-γ1, but, in B cells, only a 72 kD tyrosine phosphorylated protein strongly co-precipitated with PLC-γ2. We conclude that activation of antigen receptors in human B and T cells induces translocation of PLC-zγ isozymes to different phosphoprotein ligands in the particulate fraction.