The purpose of the paper was to study the morphological effects of retinoids on non-transformed cells such as thyrocytes. The formation of follicles was studied in primary cultures of porcine thyrocytes by adding retinol and thyroid stimulating hormone (TSH) to cells grown in the absence of TSH to form monolayers. The proliferation and apoptosis of thyrocytes were studied in cells both grown adherent to plastic surfaces and in suspension. Standard medium with traces of retinol and the same medium without retinol were used. Retinol alone was added to thyrocytes grown in the absence of TSH (TSH [symbol: see text] culture) or both retinol and TSH were added to cultures after stimulation with TSH (TSH [symbol: see text] culture). The concentration was varied from 0 to 80 microM for retinol and from 0 to 13 microM for retinoic acid. At a concentration of 13 microM, the effect of retinol was similar to that of retinoic acid. At concentrations higher than 40 microM, retinol reduced the formation of thyroglobulin-immunoreactive follicles, whereas up to 13 microM retinoic acid had no obvious influence on follicle formation. The retinoids induced apoptosis under all experimental conditions. In contrast, a significant decrease in proliferation and in the formation of thyroglobulin-immunoreactive follicles was observed only in adherent cells cultured in customary medium. The decrease in functional follicles after treatment with retinol suggests a de-differentiating effect of retinoids on normal thyrocytes and is in contrast with the differentiating effect of retinoids observed in cancer cells.