In the early 1970s, Andersen and colleagues proposed that the principal excitatory pathways of the hippocampal formation were organized in a lamellar fashion. This proposition, based heavily on the physiological studies of the proponents, indicated that "a point source of entorhinal activity projects its impulses through the four membered pathway (of the hippocampal formation) along a slice or lamella, of hippocampal tissue oriented normally to the alvear surface" [Anderson P., Bliss V.P. and Skrede K. K. (1971) Expl Brain Res. 13, 222-238] and perpendicular to the long axis of the hippocampus. Andersen et al. further suggested that, "By means of this lamellar organization, small strips of the hippocampal cortex may operate as independent functional units, although excitatory and inhibitory transverse connections may modify the behavior of neighboring lamellae." The "lamellar hypothesis" of hippocampal anatomical organization has had tremendous influence on the conceptualization of hippocampal information processing and was largely responsible for prompting the establishment of the in vitro hippocampal slice technology. While the "lamellar hypothesis" was consistent with the known neuroanatomy, subsequent neuroanatomical investigations, using a variety of modern tracing techniques, have invariably demonstrated that all of the major hippocampal projections, except for those arising from the granule cells of the dentate gyrus, are much more divergent than would be consistent with a strict interpretation of the lamellar hypothesis. This has become particularly clear in ongoing studies of the intrinsic hippocampal projections using the recently introduced anterograde tracer, Phaseolus vulgaris leucoagglutinin. Citing the conclusions from several papers dealing with the anatomical organization of the hippocampal formation and using examples from recent Phaseolus vulgaris leucoagglutinin mapping studies, the following are demonstrated. (1) That the major hippocampal projections are as extensive and highly organized in the long or septotemporal axis of the hippocampus as in the transverse axis. (2) That at least some of the hippocampal projections, such as the associational projections arising from the dentate gyrus, appear to be specifically organized to integrate distant levels of the hippocampal formation. (3) That the physiological data of Anderson et al. can be re-interpreted in the light of these new anatomical data to show how the stimulation and recording protocols used at the time would, in fact, generate the appearance of a lamellar organization. It is concluded that it is heuristically most reasonable to consider the hippocampal formation as a three-dimensional cortical region with important information processing taking place in both the transverse and long axes.(ABSTRACT TRUNCATED AT 400 WORDS)