Summary.Comparisons of the Protozoa and Metazoa have emphasised their structure‐function relationships without due regard to their historical relationships. Thus cellularity has been a common basis for this comparison as applied to unicellular organisms on the one hand and multicellular organisms on the other, equating in each group the cell as the unit of structure and function; or, on the contrary, denying that this comparison holds since Protozoa are to be regarded as non‐cellular organisms.It is proposed that genetic history, including both ontogeny and phylogeny, is the essential basis for this comparison. Since organic differentiation is the process by which the cell originated in phylogeny and each organism develops in ontogeny, maintaining its organismal unity throughout, it is suggested that primarily this process, protoplasmic differentiation, and secondarily its product, the primordial cell, should be given first importance in fundamental considerations of both protozoan and metazoan genetic history.Protozoa as well as Metazoa begin their life cycle as a primordial cell which is the stage of minimal protoplasmic differentiation. From this primordial stage comes to be differentiated epigenetically diverse organs with specific functions, derived for the Metazoa during numberless mitotic divisions but for the Protozoa during one mitotic division and are rederived during each succeeding division. Thus, Protozoa retain the capacity to reorganise, that is, to dedifferentiate and redifferen‐tiate, which they tend to do during fission, conjugation, endomixis, cystment, and regeneration; and are accordingly potentially immortal. Metazoan ontogeny, however, proceeds toward a fixed and irreversible state of differentiation which eventuates in disintegration and death.It is postulated further that protoplasmic reorganisation involves both cytoplasmic and nuclear structures which alike undergo a redifferentiation following dedifferentiation toward a primordial stage which represents the initial stage of the life cycle. While these changes may differ, with respect to the cytoplasm and nucleus, in the time, manner, or completeness of their occurrence; it is suggested that their visible manifestations have to do with dynamic processes which are fundamentally the