Retinoic acid (RA) has been shown to inhibit the differentiation of 3T3 adipogenic cell lines. In this report, the steady-state levels of several adipose-specific mRNAs were studied in mature adipocytes treated with RA. Northern blot analysis showed that, following a 24-h exposure of 3T3-F442A adipocytic cultures to RA (10 microM), there was a 4-5-fold decrease of adipsin mRNA level. In contrast, actin, adipocyte P2, lipoprotein lipase, and glycerophosphate dehydrogenase mRNA levels were unchanged during the same interval. The rate of adipsin and actin gene transcription, assessed by nuclear run-on assays, remained unchanged in adipocytes exposed to RA. The half-life (t1/2) of adipsin mRNA, determined by pulse-chase with [3H] uridine, was greatly shortened in RA-treated adipocytes (t1/2 approximately 7.3 h) as compared with untreated cells (t1/2 approximately 37.6 h). Conversely, actin mRNA stability was not altered by the drug. These results suggest that RA can specifically down-regulate adipsin expression in adipocytes at a posttranscriptional level without inducing the reversal of adipocyte differentiation.