Pycnogenol (PYC) is a procyanidin-rich extract of the bark of French maritime pine (Pinus pinaster) with a potent ability to scavenge free radicals. Lysosome-rich fractions from rat renal cortices were incubated with varying amounts of PYC and challenged with noxious doses of ﬂuoride. Controls were also included. The release of N-acetyl-β-d-glucosaminidase (NAG) isozymes in the supernatant was estimated by spectrophotometric methods. The protein content of the renal cortex was also determined. Our results show that ﬂuoride in unhealthy doses can cause a concentration dependent release of N-acetyl-β-d-glucosaminidase (NAG) isozymes from the renal lysosomes. This may be related to its known ability to initiate free radical formation or direct damaging effects on the lysosomal membrane. As a blend of bioﬂavonoids pycnogenol has a potent ability to scavenge free radicals. In our study PYC was effective in preventing ﬂuoride induced release of NAG isozymes from the renal lysosomes. Copyright © 2004 John Wiley & Sons, Ltd.