The marked gender influence on the occurrence of systemic lupus erythematosus (SLE) indicates that genetic and hormonal factors may be important in the etiology of this illness. However, few differences in clinical manifestations between males and females have been reported. To further investigate gender differences in SLE, the prevalence of 23 clinical manifestations of SLE were compared in a cohort of 62 men and 299 women. After adjusting for differences in age, race, and duration of followup, men were found to more commonly have seizures (odds ratio = 1.65; 95% confidence interval = 1.09, 2.49), and showed a trend to progress to renal failure more often (odds ratio = 1.40; 95% confidence interval = 0.96, 2.03) than women. Gender differences were not evident for the remaining 21 clinical features. The clinical similarity between men and women with SLE represents a circumstance in which the use of clinically defined patient subsets does not appear to facilitate the investigation of potential pathogenetic or etiologic factors.