Progressive loss of organogenic totipotency appears to be a common event in long-term plant tissue eultme. This loss of totipotency, which has been proposed to be a typical trait of plant neoplastic progression, is compared to some mechanisms thai occur during the establishment of animal differentiation-resistant cancer lines in ~itro. Evidence is presented that alteration in DNA methylation patterns and expression of genes occur during long-term callus culture. An effect of the auxin, 2,4-dichlorophenoxyacetic acid, in the progressive methylation, is moreover suggested. Methylation of genes relevant to cell differentiation and progressive elimination of ceils capable of differentiation is proposed as being responsible for this progressive loss of organogenic potential. Finally, the epigenetie alteration (DNA methylation) that occurs during prolonged periods of culture may induce other irreversible genetic alterations that uhimately make the loss of totipotency irreversible.