Four patients with systemic lupus erythematosus had normal findings of urinalysis and essentially normal renal function. Light microscopy studies of renal biopsy specimens revealed minimal abnormalities in three cases and early lupus nephritis in the fourth case. All four biopsy specimens had strongly positive immunofluorescence reaction with fluorescein isothiocyanate conjugated goat antihuman IgG and β1C globulin. Three of these patients later developed clinical signs of lupus nephritis in spite of treatment with steroids. This study indicates that positive immunofluorescence can be the earliest definite sign of renal involvement in systemic lupus erythematosus.