Twenty-two patients with severe long-standing rheumatoid arthritis were treated with oral zinc sulphate in a prospective long-term open trial. Six patients had (only subjective) improvement during the first 6 months of treatment, but all deteriorated subsequently. The remaining 16 deteriorated or did not improve and these patients expressed a wish to stop taking the drug after a mean period of 5 months. In the whole group of 22 patients, neither the number of affected joints, the ARA grading, nor functional classification changed significantly, nor did ESR, haemoglobin, haematocrit, or platelet count. The unpleasant taste and nausea caused by zinc sulphate was the main side effect. Our study confirms that ZnSO4 has no long-lasting beneficial effect for patients severely affected with rheumatoid arthritis.