FOXO forkhead transcription factors play an important role in controlling lymphocyte activation and proliferation. To evaluate the possibility that FOXO transcriptional expression is dysregulated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients, we determined the quantities of FOXO1, FOXO3a, and FOXO4 transcripts in peripheral blood mononuclear cells (PBMCs) from normal controls as well as from SLE and RA patients. Results showed that FOXO1 and FOXO3a are dominant FOXO factors at the transcript level in PBMCs. Statistical analysis showed that the FOXO1 transcript levels in RA patients and in SLE patients with active disease activity were significantly lower than those in normal controls, and the FOXO1 transcript levels were inversely correlated with lupus disease activity. In contrast, the differences in FOXO3a and FOXO4 transcript levels between normal controls and patients were not significant. These data suggest that the transcriptional dysregulation in FOXO1 is possibly linked to the pathogenesis of SLE and RA.