Aggregates of mast cells and lymphocytes have been found in inflamed tissues suggesting that lymphocytes may have the ability to activate mast cells through cell-to-cell contact. To examine this hypothesis, murine mast cells were transfected with a T cell activation gene-3 (TCA3)-chloramphenicol acetyl transferase (CAT) construct, and these cells co-cultured with murine EL-4 (T), CH12.LX (B), WEHI-3 (myelomonocytic) or 3T3(fibroblast) cell lines. Co-culture of activated EL-4 or CH12.LX cells, but not WEHI-3 or 3T3 cells, with transfected mast cells induced a 5 to 7 fold increase in CAT expression which was dependent on the lymphocyte to mast cell ratio. Supernatants from activated EL-4 or CH12.LX cells did not induce CAT expression in transfected mast cells. These data demonstrate that activated lymphocytes have the ability to induce the promoter of the TCA3 gene in mast cells through a mechanism requiring cell-to-cell contact, and suggest the possibility that activated lymphocytes may effect other biologic processes in mast cells as well through such heterotypic activation.