Differentiation of the human teratocarcinoma derived cell line, PA-1, with retinoids was examined at concentrations (10-6-10-8 M) that did not exhibit an antiproliferative effect during log-phase growth. Treatment with naturally occurring retinoic acid or certain synthetic retinoids (13-cis retinoic acid, Ro10–9359, and Ro13–7410), while not significantly altering the logphase growth rate, decreased the saturation cell density and mitotic indices after confluence. Retinoid treatment also induced changes in cell morphology, which appear to be related to reorganization of microtubules and microfilaments. Following retinoid treatment, the expression of cell glycoproteins (of 162 kDa, 152 kDa, 143 kDa, and 51 kDa) was altered. Treated cells also exhibited decreased expression of alkaline phosphatase, as well as an increased capacity for intercellular communication as evidenced by gap-junctional transfer of the phosphorylated toxic intermediate of 6-thioguanine to HPRT- cells. Treatment with retinoic acid dramatically reduced the quantity of shed plasma membrane material and altered its composition. © 1990, International Society of Differentiation. All rights reserved.