Antigenic or mitogenic stimulation of T cells induces the secretion of an array of protein hormones that regulate immune responses. Molecular cloning has contributed strongly to our present understanding of the nature of this regulation. A complementary DNA (cDNA) library prepared from a cloned concanavalin A-activated mouse T-helper cell line was screened for abundant and induction-specific cDNA's. One such randomly chosen cDNA was found to encode mouse preproenkephalin messenger RNA (mRNA). Preproenkephalin mRNA represented about 0.4 percent of the mRNA in the activated cell line but was absent in resting cells of this line. Other induced T-helper cell lines have 0.1 to 0.5 percent of their mRNA as preproenkephalin mRNA. Induced T-helper cell culture supernatants have [Met]enkephalin-immunoreactive material. The production by activated T cells of a peptide neurotransmitter identifies a signal that can potentially permit T cells to modulate the nervous system.