Glomerular extracellular matrix accumulation may derive from the stretching of mesangial cells caused by excessive glomerular dilatation. The relationship of glomerular volume (V-G) to intraglomerular pressure, expressed as compliance or as mean V-G in the isolated, perfused rat glomerulus, was used to analyze factors that regulate V-G. Glomeruli were highly distensible over the normal and relevant abnormal range of pressure. Compliance increased directly with basal V-G (P < 0.001), i.e., larger glomeruli dilated more than smaller ones at any given pressure. Perfusion with atrial natriuretic peptide did not alter compliance, and inhibitors of nitric oxide synthesis exerted only a trivial effect. V-G expansion was consistently reduced by angiotensin II, but this effect was small (3.8%, P < 0.001). After subtotal nephrectomy, compliance increased by 59% in the remnant glomeruli (P < 0.001); 22% of this increase was attributable to structural changes, and the remainder was attributable to the large basal V-G of the hypertrophied glomeruli. Thus the major determinants of V-G expansion include capillary wall tension, basal V-G, and intrinsic distensibility, which is markedly influenced by the character of the extracellular matrix and only slightly altered by an angiotensin II-modified mesangial cell tone.