The immunohistological expression of integrins and CD44 cell adhesion molecule was analyzed on neuroblastoma (NB) specimens to study the potential role of these molecules in normal differentiation and in the transformation of neural crest derivatives. None of the specimens expressed the alpha 5 beta 1 integrin heterodimer; the expression of alpha 3 beta 1 heterodimer was maintained during all stages of differentiation; alpha 1 beta 1 heterodimer was expressed on undifferentiated neuroblasts and on Schwann cells, but was lost on ganglion cells. In contrast alpha 2 beta 1, alpha 6 beta 1, alpha 6 beta 4 and alpha V beta 1 expression was usually restricted to cells differentiated in the Schwann cell lineage. Alpha V beta 3 was expressed on tumors developed in the mediastinum. CD44 was strongly detected on differentiated ganglioneuroblastomas, stage 1 and 2 ganglioneuromas, as well as low-grade stage 4S NB and normal neuroblasts migrating in the fetal adrenal gland. CD44 expression was observed on Schwann cells and ganglion cells; in contrast, it was expressed on only 50% stage 3 and 4 undifferentiated NB. None of these specimens expressed exons V5, V7 or V6. In a few specimens, an intracellular expression of exons V8-V10 was observed in ganglion cells. The expression of CD44 on NB may reflect its pattern of expression on sympatho-adrenal precursors and arrest differentiation at these stages. Conversely, CD44 expression may be silenced during malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS)