In mouse 3T3-L1 preadipocytes, the glucocorticoid dexamethasone has been shown to promote a switch in β-adrenoceptor subtype expression from β 1 to β 2 and to increase the total number of β-adrenoceptors. The present study demonstrates that sodium butyrate also modulates β-adrenoceptor expression in these cells. Incubation of preadipocytes with 2–10 mM butyrate for 24–48 h promoted a dose- and time-dependent switch in β-adrenoceptor subtype from a near equal mixture of β 1 and β 2 to > 85% β 2 and caused an approximate doubling of the receptor number. β-Adrenoceptors were assayed in membranes prepared from 3T3-L1 cells using the radiolabeled antagonist [ 125I]iodocyanopindolol and the β 2-selective antagonist ICI 118.551. Other short chain acids were not as effective as butyrate in promoting changes in β-adrenoceptor expression. Cycloheximide (1.0 μg/ml) inhibited the effects of butyrate on both β-adrenoceptor subtype and number. Alterations in β-adrenoceptor phenotype promoted by either butyrate or dexamethasone were functionally correlated with cAMP accumulation in these cells. Comparison of the effects of butyrate and dexamethasone on β-adrenoceptor expression suggests that these two agents regulate β-adrenoceptors by different mechanisms.