The degradation of the lipid peroxidation product 4-hydroxynonenal (HNE) in primary cultures of kidney tubular and mesangial cells was determined. Using various initial concentrations of the aldehyde a decline of cellular viability was found. Mesangial cells were more susceptible to the toxic effects of HNE. In consumption studies of HNE the decline of the exogenously added aldehyde was comparable in both cell types after addition of 10 and 1 µmol HNE/l. After addition of 100 µmol/l aldehyde a drastically lower HNE degrading capacity was found in mesangial cells as compared to tubular cells. The loss in the HNE degrading capacity was accompanied by an increased formation of HNE-protein aggregates as demonstrated by immunoblots. Therefore, we concluded that the low ability of mesangial cells to degrade HNE may be a factor of the toxicity of free radicals on the kidney.