TISlO is a primary response gene whose cDNA was cloned as a result of its rapid, superinducible expression in Swiss 3T3 cells in response to 12-0-tetradecanoylphorbol-13-acetate. The 5” untranslated region of the 3.9-kilobase TISlO message contains only 124 nucleotides, whereas the 3 “untranslated region is almost 2 kilobases in length. Within this long 3’region, there are multiple repeats of the sequence ATTTA, a sequence often present in rapidly degraded mRNA species. Primer extension revealed that the TISlO cDNA begins 16 base pairs downstream of the transcription start site for the TISlO gene. The TISlO cDNA encodes a predicted protein of 604 amino acids. A computer search identified striking similarities between the predicted TISlO protein product and the murine, sheep, and human prostaglandin synthase/cyclooxygenase proteins. The TISlO protein has many of the same conserved amino acids that are thought to be important for cyclooxygenase function, TISlO mRNA is undetectable by Northern analysis in quiescent 3T3 cells. The TISlO gene is rapidly and transiently induced by forskolin and serum, as well as by 12-0-tetradecanoylphorbol-13-acetate, in Swiss 3T3 cells. These agents elicit far more dramatic changes in TISlO mRNA levels than in cyclooxygenase mRNA levels. The expression of the TISlO gene appears to be highly cell type-restricted in cultured cell lines; of 12 cell lines tested under superinducing conditions, only the rodent embryonic Swiss 3T3 and Rat1 cell lines expressed TIS 10 gene.