Class IV is the most common form of lupus nephritis (LN). This class is divided into diffuse segmental active subclass (IV-S/A) and diffuse global active subclass (IV-G/A). The purpose of the study was to compare the clinical data, and the incidence of glomerular active features in IV-S/A, and IV-G/A of LN. Of 34 patients with class IV LN, 25 were classified as subclass IV-G/A, and 9 patients were included in subclass IV-S/A. Nephrotic syndrome and hypertension were significantly more frequent in patients in the IV-G/A subclass, whereas hematuria and low grade proteinuria were significantly more frequent in patients in the IV-S/A subclass. Immunofluorescence findings revealed in group IV-S/A the presence of mesangial deposits and sparse deposits along the capillary wall. In contrast, an immunofluorescence study in subclass IV-G/A showed a preponderance of great subepithelial deposits. Fibrinoid necrosis of glomerular tufts was significantly more evident in subclass IV-S/A, whereas endocapillary hypercellularity, hyaline thrombi and wire loops were more frequent in subclass IV-G/A. The significant differences in clinical manifestation and in the incidence of histopathological active glomerular features between subclasses IV-S/A and IV-G/A of LN observed in our study may confirm the suggestion that these lesions have a different pathogenesis.