Abstract-Effects of D-penicillamine-L-cysteine disulfide (P-C) on some immunological parameters were examined in normal and immunity-impaired mice and rats. P-C enhanced the DNA synthesis in concanavalin A-stimulated mouse spleen cell cultures in vitro. In vivo, administration of P-C produced either enhancement or depression of plaque forming cell (PFC) response and delayed type hypersensitivity (DTH) to sheep red blood cells (SRBC) in low responder mice to SRBC, depending on the dose of P-C. P-C restored the impaired PFC response in hydrocortisone-pretreated mice. The enhancing effect of P-C was not shown in high responder mice to SRBC, but an in hibiting effect was observed. P-C inhibited the suppressor cell induction on PFC response in mice immunized with a supraoptimum dose of antigen. In adjuvant arthritic rats, P-C induced severe arthritis by eliminating the suppressor cells regulating this disease process. The relevance of these findings and mode of action of D-penicillamine in rheumatoid arthritis is discussed.