In 3 patients, two 26 and one 29 years of age, a nephropathy was accidentally discovered which progressed to end stage renal failure within 4 to 6 years. Renal biopsy revealed an unusually marked karyomegaly particularly of the tubular epithelium. These cytopathological changes were associated with chronic interstitial nephritis. Biopsies of other organs, i.e. liver, colon, bronchus and lungs indicated in 2 patients a systemic distribution of the karyomegaly, particularly in mesenchymal cells. Neither the chronic interstitial nephritis nor the karyomegaly could be ascribed to a recognized etiology. This suggests, therefore, that there is a relationship between these changes. The karyomegaly could be the result of the action of some antimitotic agent such as chemical toxins or virus infections.