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Examples are provided where this type of information can reveal the mechanism of pharmacokinetic processes at the submolecular level. The role of lipophilicity in quantitative structure\u2013activity relationship (QSAR) studies of opioids is reviewed. The physicochemical properties and pharmacology of the main metabolites of morphine are also discussed. Recent studies indicate that the active metabolite morphine\u20106\u2010glucuronide (M6G) can contribute to the analgesic activity of systemically administered morphine. The unexpectedly high lipophilicity of M6G partly accounts for its analgesic activity. When administered parenterally, another suspected minor metabolite, morphine\u20106\u2010sulfate (M6S) has superior antinociceptive effects to those of morphine. 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