Different chronic states of mesangial cell contraction were induced by variation of extracellular volume in Munich-Wistar rats for 6 days to study the influence of mesangial cells on the geometry of the glomerular tuft. Stereological analysis of superficial glomeruli in volume-expanded rats (VE, treated with enalapril) and volume-reduced rats (VR, treated with indomethacin) revealed a glomerular tuft volume 28.7% smaller, and a capillary luminal volume 32% smaller in VR than in VE rats. The filtration area [defined as glomerular basement membrane (GBM) area facing fenestrated endothelium] was greatly reduced in VR rats (97 +/- 16 X 10(3) micron 2 vs 137 +/- 13 x 10(3) micron 2). The surface density (Sv) of the GBM was higher by approximately 10% in VR rats primarily due to the considerable increase in Sv of the perimesangial GBM subdivision (0.189 +/- 0.01 micron 2/micron 3 vs 0.153 +/- 0.01 micron 2/micron 3), indicating a higher degree of mesangial cell contraction in these animals. Our results suggest (1) that mesangial cell contraction plays a major role in the adaptation of the glomerular tuft to variations in extracellular volume; (2) that the relevance of mesangial cell contraction for the regulation of glomerular haemodynamics appears to be small; and (3) that the reduction in filtration area, although prominent, cannot fully account for the considerable decreases in the ultrafiltration coefficient observed by others in acute and chronic studies.