The transfer of albumin from blood to tissue has been found to be increased in caveolin-1 knockout (KO) mice. This has been considered to reflect increased microvascular permeability, conceivably caused by an increased endothelial production of nitric oxide (NO) in these mice. To investigate whether such an increase in NO production would also affect glomerular barrier characteristics, the glomerular sieving coefficients (theta) to neutral FITC-Ficoll 70/400 (molecular radius 13-90 A) were determined in caveolin-1 KO mice vs. their wild-type counterparts. The theta for Ficoll were assessed using high-performance size-exclusion chromatography on blood and urine samples. Furthermore, the transcapillary escape rate (TER) of (125)I-labeled albumin and plasma volume (PV) were determined in both types of mice. The kidney expressed low levels of caveolin-1 compared with the lung and bladder, but immunofluorescence associated with vascular structures was evident. Staining was lost in the caveolin-1 KO kidney, as was caveolin-1 expression in the lung and bladder. Despite an increase in the glomerular filtration rate in caveolin-1 KO mice (0.23 +/- 0.04 vs. 0.10 +/- 0.02 ml/min; both n = 7; P < 0.05), the glomerular Ficoll sieving curves were nearly identical. Furthermore, caveolin-1 KO mice showed an increased PV (6.59 +/- 0.42 vs. 5.18 +/- 0.13 ml/100 g; P < 0.01) but only a tendency toward an increased TER (14.69 +/- 1.59 vs. 11.62 +/- 1.62%/h; not significant). It is concluded that in caveolin-1 KO mice the glomerular permeability was not increased, despite the presence of glomerular hyperfiltration. The present data are in line with the concept that the increased transvascular albumin leakage previously found in mice lacking caveolin-1 may be due to an elevation in systemic microvascular pressure due to precapillary vasodilatation, rather than being a consequence of increased microvascular permeability per se.