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To determine definitively whether or not the severity of the Mazzotti reaction was correlated with infection intensity, as determined by skin snip quantification, 21 infected Ghanian patients were evaluated during 7 days of treatment with 200 mg/day of diethylcarbamazine. Serial blood, urine and skin biopsy samples were collected during the progression of the Mazzotti reaction. Hypotension, fever, adenitis and pruritus were all correlated with infection intensity in these patients while arthralgia and tachycardia were not. Peripheral blood eosinopenia and neutrophilia also correlated with intensity of infection and appeared to reflect the accumulation of degranulating eosinophils around “mobilized” microfilariae that migrated from the dermis to the epidermis after diethylcarbamazine (DEC). Other mobilized microfilariae apparently were cleared by the liver and resulted in abnormal liver enzyme levels in the serum which, again, were directly correlated with the patients' microfilarial density. Though the severity of the Mazzotti reaction clearly correlated with intensity of infection, the different times of onset of symptoms, and cellular and serum chemistry changes indicate that there are probably multiple infection intensity-dependent mechanisms responsible for mediating this complex reaction.