The concurrent presence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) ("rhupus" or "rufus") has been described in the literature. However, it has not been clear to what extent and under what circumstances clinical disease expresssion can undergo transitions from one disease to the other. We postulated that major hormonal events might have an influence on disease expression in such patients and conducted a retrospective study of 1507 patients with RA and 893 with SLE. In this population, 13 patients were identified as having convincing clinical diagnoses of both RA and SLE. Although 6 of these 13 patients had symptoms and signs of RA and SLE concurrently during their entire illness, 7 patients had clearly identifiable transitions from SLE to RA, and in one of these patients the reverse occurred as well. Of the 7 transitions from SLE to RA, 5 were associated with menopause (3 of these patients were receiving hormone replacement therapy) and the other 2 occurred in the postpartum period. The one change from RA to SLE in this series occurred during pregnancy. Thus, pregnancy, the postpartum period, and menopause can modulate disease expression in patients with both SLE and RA. It is speculated that, in patients with an autoimmune predilection, a high-estrogen environment (premenopause, pregnancy) favors the clinical expression of SLE, whereas a low-estrogen environment favors more RA-like disease, possibly because of the immunomodulatory effects of sex-steroids. The clinical implication is that in the management of patients with autoimmune diseases such as SLE and RA, hormonal alterations could result in changes in disease expression that might necessitate changes in treatment.