Investigation of these hypotheses in man is difficult. While local skin changes to intradermal NAC have been used to examine dose-response in patients, this approach does not lend itself to detailed investigation of the underlying mechanism and cannot be used to explore the effect of high paracetamol concentrations. We propose to use an alternative well-established model previously used by us to investigate the mechanisms involved in the pharmacodynamics of morphine in man by the measurement of forearm blood flow and skin response following intra-arterial infusion. The proposed model allows administration of doses far smaller than those used systemically and thus minimises the risk of unwanted systemic effects from either NAC or paracetamol. Safe administration of intra-arterial NAC (up to 300 mg/min, greater than that intended here) has previously been demonstrated. Local changes can be used as a surrogate for systemic effects, as described previously.