IL-2 mRNA has a t1/2 of 1 to 2 h in T lymphocyte cell lines and in activated human PBL. Human Jurkat cells show a rapid increase of IL-2 mRNA on induction of IL-2 synthesis, followed by an equally rapid decline 4 to 6 h later. The decline occurs despite a high rate of synthesis, and appears to be due to an enhanced rate of IL-2 mRNA degradation. The degradation of IL-2 mRNA is selectively sensitive to cycloheximide and actinomycin D, inhibitors of protein and RNA synthesis, respectively. IL-2 mRNA levels in mouse EL4.E1 T lymphoma cells, and in activated human PBL, decline rapidly on removal of the inducing agents, indicating that transcription continues only as long as the activating signal is present. The transience of IL-2 mRNA is seen as an important property of a transiently acting immunoregulatory factor.