Karyotype determinations were made on a wild Ehrlich ascites tumour and on a subline which was made resistant to daunorubicine (DNR) by long-term treatment with this drug. During the development of resistance, karyotypic alteration occurred, with a change from near-tetraploidy to hyperdiploidy and the appearance of marker chromosomes which were not found in the original tumour. The resistance was gradually lost on cessation of DNR treatment. A tumour subline which, after having been resistant, had become sensitive again, presented a karyotype resembling that of the original tumour. Another tumour which had partially lost its resistance, was composed of a mixture of cells with karyotypes characteristic either of the sensitive or of the resistant tumour. It had been found previously that the rate of growth in the resistant tumour was lower than that observed in the sensitive one. The loss of resistance was explained by abundant growth of sensitive cells present in the resistant tumour. The possibility of checking loss of resistance clinically by examining the karyotype of the malignant cells is discussed.