D -Penicillamine, a reducing and chelating agent used in the treating of rheumatoid arthritis, was tested for its effects of polymorphonuclear leukocyte chemotaxis, phagocytosis, and lysosomal enzymes. beta-Glucuronidase release from polymorphonuclear leukocytes after phagocytosis of latex particles was not affected by D-penicillamine at concentrations ranging from 25 to 400 mg/liter. No direct effect was seen on enzyme activity at the maximum concentration of the drug. There was no inhibition of latex particle ingestion. No cell damage was found at 400 mg/liter penicillamine as measured by lactic dehydrogenase release. At this drug concentration there was only a 15% reduction in hemolytic complement levels. Chemotaxis was significantly decreased at concentrations of 50 mg/liter with a dose-dependent effect at higher concentrations which showed a plateau from 200 to 400 mg/liter. The parent compound D-cysteine was also tested in these systems. The same lack of effect of phagocytosis and enzyme release was found. D-Cysteine did inhibit chemotaxis but to a lesser degree than D-penicillamine. This dicotomy of drug effect may indicate that the beneficial action of D-penicillamine in the treatment of rheumatoid arthritis is due to the decreased chemotaxis of polymorphonuclear leukocytes into the joint, while the absence of an effect of phagocytosis and lysosomal enzymes shows the cells can still function to ingest and destroy bacteria. This latter effect correlates with the absence of infection in patients treated with this compound.