Measurements were made of the neutral proteoglycan-digesting protease activity in the cartilage matrix breakdown observed in the rheumatoid arthritic process. Normal knee (tibial plateau) cartilage specimens were obtained from 7 fresh cadavers and 29 cartilage specimens were obtained from 23 patients diagnosed as having rheumatoid arthritis (RA). The total neutral metalloproteoglycan-degrading enzyme (NMPE) activity in RA cartilages exhibited roughly an eightfold elevation over that of control subjects. The active form of the NMPE for diseased cartilage was higher than that observed for normal cartilage, but was not statistically different. A very low level of activity was detected for serine proteases and no variation was observed between normal and diseased cartilages. Data obtained from RA cartilages were also analyzed with respect to the relationship between enzyme activities and the patients' medications. Four groups of patients were then selected according to their drug treatments: S + G patients received steroid and gold therapy; S patients received steroids only; NS + NG patients did not receive steroid or gold therapy; G patients received gold therapy alone. The total NMPE activity for each of these groups remained at a very high level. The active enzyme activity measured in S + G and S patients was decreased to a level not different from that of normal controls. Specimens from NS + NG patients presented a significantly higher level of the active form of the enzyme (P less than 0.05) when compared with either normal controls, S + G, or S patients. No significant difference was noted in the level of serine protease activity between the RA cartilage and normal cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)