Objective. To evaluate CD4+ T cell counts of rheumatoid arthritis (RA) patients at 18 and 30 months after treatment with a chimeric anti‐CD4 monoclonal antibody (MAb), cM‐T412, in a phase I trial. Methods. Of the 25 RA patients who received the MAb, 23 were available for followup at 18 and 30 months. Levels of circulating CD4+ T cells were measured by flow cytometry. Results. Circulating CD4+ T cell levels in these 23 RA patients remained below normal at 18 and 30 months posttreatment. More profound CD4+ T cell depletion was noted in the higher‐dose groups (300 and 700 mg). Conclusion. Prolonged suppression of circulating CD4+ T cells was noted both in single‐infusion and multiple‐infusion groups 18 and 30 months after cM‐T412 treatment. The depression was more pronounced in patients who received multiple infusions of cM‐T412. The prolonged decrease in CD4+ T cell numbers suggests that the capacity to reconstitute CD4+ T cells in this patient population (treated with methotrexate) is limited. One patient, who was also receiving methotrexate and prednisone, died 18 months after receiving 100 mg of cM‐T412. No other significant adverse effects, in particular, no opportunistic infections, were reported in these 23 RA patients at 18 and 30 months of followup.