Pathological hyperbilirubinemia in the neonate is a serious problem that can lead to a spectrum of neurological consequences from mild deficits to death secondary to kernicterus. An effective chemopreventive therapy that could be given to high risk infants would allow a proactive approach, provide a level of control not currently available, and circumvent some of the limitations of phototherapy and exchange transfusion. A key target for such therapy is heme oxygenase (HO), the rate limiting enzyme in the heme catabolic pathway. Metalloporphyrins, synthetic derivatives of heme, are competitive inhibitors of HO, and meso-, deutero-, and proto- derivatives with various metal substitutions including tin (Sn), zinc (Zn), and chromium (Cr) have been studied as potential therapeutic agents. Current selection of these compounds is based upon potency of inhibiting HO, phototoxicity, and various other pharmacologic parameters. However, there are still many unknown properties of metalloporphyrins which require further investigation. We examined the effects of these compounds on the level of transcription of the HO gene. We have developed a rapid transcriptional assay for HO expression using a luciferase gene fused to the HO-1 promoter such that light is emitted in proportion to promoter activity in living cells in culture. Using this technique, we are able to study the effects of metalloporphyrins on the level of transcription in real time. Our initial studies have shown that although metalloporphyrins inhibit HO activity, they also increase the rate of transcription of the HO gene which may have significant implications for therapeutic use of these compounds. The ability to follow the transcription level in living cells combined with our ability to measure HO activity and cytotoxicity over time may facilitate metalloporphyrin selection. Ultimately, engineering a transgenic mouse through incorporation of the HO-luciferase gene will enable us to study the effects of these metalloporphyrins in the intact animal, in real time, in hopes of establishing which of the metalloporphyrin compounds is best suited for clinical therapy.