Systemic lupus erythematosus (SLE) is characterized by periods of flare and remission. The search for parameters associated with disease activity has been an area of intense investigation. To identify genes that best differentiate patients with active from those with inactive disease, the expression pattern of 375 genes was analyzed in peripheral blood mononuclear cells (PBMC) from 12 patients with active and 14 patients with inactive disease. Using the "nearest shrunken centroids" method, 29 genes were found to best discriminate the two groups. Among these genes, 14 were upregulated and 15 were downregulated in patients with active compared to those with inactive disease. Fourteen of these genes also correlated with SELENA-SLEDAI with correlation coefficients ranging from 0.4 to 0.7. Most of these genes have not been previously associated with disease activity and belong to a variety of families such as adhesion molecules, proteases, TNF superfamily, and neurotrophic factors. Using a cross-validation method, the error rate for classifying samples in the two groups was 30%. These results highlight the potential use of microarray data in identifying genes associated with disease activity in SLE, which could become potential biomarkers or future therapeutic targets.