To examine associations between serum macrophage migration inhibitory factor (MIF) and disease-related variables and corticosteroid use in patients with systemic lupus erythematosus (SLE). Serum MIF concentration was measured by ELISA in 90 female patients with SLE and 279 healthy controls. Univariate and multivariate regression analyses were used to examine the associations between serum MIF concentration and disease-related indices of SLE and corticosteroid use. Serum MIF concentrations were positively associated with SLE disease damage (SLICC/ACR index), and indices of disease damage were greater in SLE patients with serum MIF concentrations above the normal median value. Serum MIF concentration was also observed to be significantly greater in patients with SLICC/ACR damage index (DI) scores >/= 3. Serum MIF was also positively associated with current corticosteroid dose. Significantly higher SLICC/ACR DI scores were observed in patients with values of serum MIF above the normal median, and this remained significant after adjusting for corticosteroid dose. Serum MIF concentration was also predictive of SLICC/ACR index after 3 years of followup, but this association was partly confounded by corticosteroid dose. Serum MIF was also negatively associated with serum creatinine concentration, independent of disease damage and corticosteroid dose. MIF is overexpressed in patients with SLE. While this can be partly explained by corticosteroid use, there is evidence of an association between MIF and lupus-related disease damage.