We retrospectively analyzed the relationship between rheumatoid factor (RF) and renal disease in 102 patients with systemic lupus erythematosus (SLE). We found a significant negative association between detectable RF at any time in a patient's course and clinically significant renal diseases. Multivariate analysis indicates that RF and cryoglobulins, operating independently, have a significant and opposite association with the development of renal disease in patients with SLE. These associations appear to be unrelated to the presence or absence of anti-ds-DNA (anti-DNA). Patients with SLE who are RF negative and cryoglobulin positive are likely to develop renal disease whereas those who are RF positive and cryoglobulin negative are very unlikely to do so. The addition of RF and cryoglobulin determinations to the data base of patients with SLE appears to be clinically useful.