Peripheral blood mitogen-induced cellular cytotoxicity (MICC) was studied in 13 untreated patients with active rheumatoid arthritis (RA; group A) and in 5 RA patients with inactive disease (group B), using phytohemagglutinin (PHA) as stimulating agent and K562 cells as target cells in the chromium-51 release assay. MICC was found to be significantly reduced in the patients of group A compared with normal subjects (P < 0.01) and the patients of group B (P < 0.05). No differences were noted in MICC between group B patients and normal subjects. A statistically significant negative correlation was found between values of patients' MICC and serum C-reactive protein levels (r = -0.685, P < 0.01). Furthermore, patients' MICC correlated well with patients' peripheral blood natural killer cell activity (P < 0.02), as well as with the absolute number of circulating CD8+ cells. No correlation was found between MICC and duration of disease, erythrocyte sedimentation rate, serum alpha 2-globulins, or the titre of serum rheumatoid factor in the patients studied. We concluded that defective MICC in untreated patients with active RA is probably due to the diminution of the number of CD8+ cells, although a qualitative defect of these cells cannot be excluded.