Neoplastic cells from different tumors (lung, colon, rectal, and pancreatic carcinoma, synovial sarcoma, and Wilm's tumor) were fixed on slides and in situ digested with Hpa II and Msp I restriction enzymes. Staining of samples with the DNA specific fluorochrome ethidium bromide showed a clearcut decreased fluorescence after Hpa II digestion in neoplastic cells as compared to normal controls, whereas Msp I digestion produced the same pattern in neoplastic and in normal cells. The authors hypothesize that the altered state of methylation in neoplastic cells could affect the Hpa II activity on fixed chromatin.