Adult rat hippocampal progenitor cells (AHPCs) are self-renewing, multipotent neural progenitor cells (NPCs) that can differentiate into neurons, oligodendrocytes, and astrocytes. AHPCs contact a variety of molecular cues within their surrounding microenvironment via integrins. We hypothesize that integrin receptors are important for NPCs. In this study, we have examined the distribution of integrins in neuronal-like, oligodendrocyte-like, and astrocyte-like AHPCs when grown on substrates that support integrin-mediated adhesion (laminin, fibronectin), and those that do not (poly-L: -ornithine, PLO) using immunocytochemistry as well as characterized the phenotypic differentiation of AHPCs plated on laminin and fibronectin. Focal adhesions were prominent in AHPCs plated on purified substrates, but were also found in AHPCs plated on PLO. The focal adhesions observed in AHPCs plated on PLO substrates may be formed by self-adhesion to the endogenously produced laminin or fibronectin. We have demonstrated that integrins contribute to the initial morphological differentiation of AHPCs, as inhibition of fibronectin binding with the competitive inhibitor echistatin significantly decreased the number of processes and microspikes present in treated cells, and also decreased overall cell area. Finally, we have characterized the genetic profile of a subset of integrins and integrin-related genes in the AHPCs using reverse transcriptase polymerase chain reaction. These results demonstrate an important role of integrins, in vitro, for the initial morphological differentiation of AHPCs.