The response of human T lymphocytes to various stimuli includes the expression of the matrix metalloproteinase (MMP) genes stromelysin 2, gelatinase A and gelatinase B. The proteins encoded by these genes could confer the capacity to degrade macromolecular components of the extracellular matrix (ECM), and to shed transmembrane proteins such as tumor necrosis factor (TNF), TNF receptor, Interleukin-6 receptor and Fas ligand. To identify further MMP genes transcribed in T lymphocytes exposed to phorbol 12-myristate 13-acetate and a calcium ionophore, we combined reverse transcription and polymerase chain reaction using primers specific for conserved domains and detected collagenase 3 transcripts, first described in a human breast cancer. However, when the sequence of the complementary DNA was compared, additional 23 nucleotides were found in the 5' nontranslated region of the lymphocyte messenger RNA (mRNA). Northern blot analysis revealed 2 major inducible mRNA species of 1.9 and 2.8 kilobases, whose levels were lower than those of stromelysin 2. The observation that activated T lymphocytes transcribe several MMP genes, including a collagenase, indicates that the effector functions of these cells include enzymatic activities towards most constituents of the ECM, as well as some transmembrane proteins relevant to inflammation and apoptosis.