Sequential lung function tests were performed on 17 scleroderma patients who were treated with D-penicillamine (DP) (total of 66 treatment years) and on 10 control scleroderma patients who were not treated or were treated with low-dose prednisone (total of 25 treatment years). Cusum plots showed significant differences between the 2 groups in their cumulative changes in carbon monoxide diffusing capacity (DLCO) (P less than 0.005) and in DLCO/lung volume (P less than 0.02). The end value of the DLCO was greater than 10% lower than the initial value in 3 of the 17 DP-treated patients versus 5 of the 10 control patients (P less than 0.01, Fisher's exact probability test); in 3 DP-treated patients and 8 control patients (P less than 0.003, Fisher's exact probability test), the end value of the DLCO/lung volume was greater than 10% lower than the initial value. We conclude that DP has a beneficial effect on interstitial lung disease in patients with scleroderma.