The difficulties encountered in administering D-penicillamine to 40 patients with rheumatoid arthritis (RA) over a six to 24 month period are recorded. Side-effects were frequent. Proteinuria occurred in 13 patients (33%) mainly in the fourth to the sixth month. Renal biopsies were performed in six patients and all showed light microscopy abnormalities. Electron microscopy performed in five patients revealed subepithelial deposits in all and in addition some had mesangial and subendothelial deposits. Seven patients (17.5%) developed eight episodes of thrombocytopaenia which was quickly reversed on cessation of treatment or reduction in dosage. On the positive side, there was significant improvement in most parameters of disease activity at six, 12 and 18 months compared to the pretreatment levels, but the results at two years were less impressive. Reduction in steroid dosage was considerable and was greater than half the mean pretreatment dose after two years but the absence of a control group makes the full significance of these uncertain. Patients on high and low dosage regimens were compared over a 12 month period of treatment. Although the differences were not statistically significant, withdrawals and side-effects were less frequent in the low dose group.