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Thirty-seven patients were studied before and during treatment with respect to immune status, clinical response and development of adverse effects and autoantibodies. The baseline immune status was not predictive in terms of the above features, apart from the fact that the group of 7 patients developing proteinuria had a tendency to low or subnormal IgG levels. The most marked clinical improvement was recorded in the group who had augmented skin test responses sometime during the treatment period. These patients also had the largest falls in the IgG, IgA and rheumatoid factor. Antinuclear antibody persisted or increased in titre in 38% of patients, but was not associated with poor prognosis or liability to side-effects. Autoantibodies to striational or smooth muscle occurred in 20% of patients, and there was a much higher incidence of proteinuria in this group. We have previously suggested that penicillamine may act by depressing humoral function, leading to augmentation of cell-mediated immunity. Although the present findings suggest that penicillamine does cause humoral depression in some cases, it is not clear how the drug induces the side-effects described.