Many of the nonsteroidal antiinflammatory drugs (NSAIDs) currently marketed produce severe gastrotoxic side effects. However, acetaminophen (4-hydroxyacetanilide), which is devoid of gastrotoxicity, is associated with hepatotoxicity and nephrotoxicity. Hepatotoxicity and nephrotoxicity of acetaminophen in man and experimental animals have been attributed to metabolic conversion of the drug into a reactive intermediate by the cytochrome P450 dependent mixed function oxidase system [1]. N-acetyl-p-benzoquinoneimine (NAPQI) is the most likely structure for the ultimate reactive intermediate that depletes cellular glutathione (GSH) and covalently binds to tissue macromolecules [2, 3]. Inasmuch as N-oxidation and attack by tissue nucleophiles on the oxidized aromatic ring of acetaminophen are features that correlate with hepatotoxicity, Harvison and coworkers prepared monomethylated acetaminophen analogues with the expectation that N-oxidation and or reaction with tissue nucleophiles would be hindered [4]. The reported results supported this hypothesis since N-methylation of acetaminophen completely blocks the hepatotoxic reaction [5]. Furthemore, methyl groups ortho to the amide function (2,6-dimethylacetaminophen) were found to block hepatotoxicity [3], whereas 2-methylacetaminophen was found to possess significantly lower hepatotoxicity when compared to acetaminophen [4]. However, the analgesic potency of the above-mentioned analogues seems to parallel their hepatotoxic potential, and both activities parallel the oxidation potentials in this series of compounds. In one sense this is unfortunate, since the authors of these studies had hoped to find a nonhepatotoxic analogue that was active as an analgesic. In research aimed at further understanding the mechanisms of acetaminophen toxicity, it was discovered that the regioisomer 3-hydroxyacetanilide was not hepatotoxic in mice [6 – 8] and also showed analgesic and antipyretic activity. On the other hand, a number of compounds, including the 3,4-dihydrocarbostyril [9], benzoxazolinone [10, 11], pyridinoxazolinone [12], 1,4-benzothiazine [13], pyridin1,4-thiazinone [14], and 1,4-benzoxazinone [15, 16] derivatives, have attracted attention as potential analgesic and or antiinflammatory agents. In view of the above, we considered that it might be of interest to evaluate the analgesic and anti-inflammatory activities of two derivatives of benzoxazine previously synthesized by us [17]. These compounds, since they can be viewed as cyclized versions of substituted 3and 4-hydroxyacetanilides, have frameworks similar to those of acetaminophen.