Inflammation, an acute phase stress, alters copper (Cu) metabolism, but effects on human Cu requirements are unknown. Cu supplementation (2 mg/day, 4 weeks) increased erythrocyte Cu-zinc (Zn) superoxide dismutase (SOD) activity levels in 18 of 23 rheumatoid arthritis (RA) patients receiving gold or methotrexate (mean increase 21%). SOD values were significantly lower in RA patients than in 47 age- and sex-matched controls before, but not after supplementation. Supplementation did not significantly affect ceruloplasmin (Cp) activity or protein concentrations in either group. However, RA subjects showed significantly lower Cp activity to protein ratios compared to controls, before and after supplementation. Cu supplementation did not affect acute phase status of RA patients as evidenced by unchanged serum alpha-1-acid glycoprotein levels. In conclusion, the effects of Cu supplementation on erythrocyte SOD activities suggested a trend toward marginal Cu status in RA patients.