In cultured mammalian cells, both normal and transformed, cell–cell contact was shown to alter the detergent extractability of nuclear and plasma membranes detected using immunocytochemistry of fixed cells. This alteration occurred in each cell individually, occurred in less than 1 hour after altered cell–cell contact, and did not involve new protein or mRNA synthesis. These results indicate that composition of cellular membranes is highly affected by cell–cell contact and culture density. This suggests a possible role for alterations in membrane composition in the regulation of normal cell behavior, including signaling of contact inhibition of growth and movement, behaviors that are not effectively regulated by cell–cell contact in malignantly transformed cells. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc.