Recently, nitric oxide (NO) has been implicated as an epigenetic factor in keloids, a scarring disease occurring primarily in dark skinned people who have relatively high amounts of pigment melanin. In this work, we tested whether a melanin-mediated redox reaction involving adsorbed NO and O 2 can couple NO oxidation with O 2 reduction to form reactive oxygen species (ROS) or reactive nitrogen species (RNS) in vitro at pH 7.4. We measured the formation of reactive species that oxidize dihydrorhodamine123 (DHR) to fluorescent rhodamine123 in the presence and absence of sepia melanin. In separate experiments, we monitored NO concentration with 4,5-diaminofluorescein (DAF) by measuring the highly fluorescent NO-adduct, DAF-2T. We attempted to detect peroxynitrite with 5 µM 3-methyl-1,2-cyclopentanedione (MCP), a selective scavenger of peroxynitrite (IC50 = 3.6 µM for ONOO vs. 63.8 µM and >> 100 µM for NO and respectively). However, MCP itself oxidized DHR. We found that in the absence of NO, melanin itself oxidizes DHR, with no loss of DAF-fluorescence (i.e. no net consumption of NO). In the presence of NO, there was a ~57% loss of DAF fluorescence, indicating that NO x is formed at the expense of NO. The data provided good fit (r 2 = 0.94) to a Langmuir adsorption isotherm, with pseudo first order rate k' = 8.2 × 10