The effects of cAMP-analoguedibutyryl- AMP and anticalmodulin W-7 were studied on de novo synthesis and secretion of lipids in cultures of hepatoma Mc- Ardle RH7777 cells and normal rat hepatocytes. Dibutyryl-cAMP and W-7 separately caused a significant decrease in the secretion of de novo synthesizedtriacyl [3H] glycerolin both cultures of Mc Ardle cells and rat hepatocytes. The inhibitory effects of dibutyryl-cAMP and W-7 were concentration-dependent and appeared at the lowest concentration examined, 5µM and 20µM respectively. Dibutyrylc AMP at a concentration of 50 µM andW-7 (20 µM) suppressed the secretion of triacylglycerol by approx. 38% (p<0.05) and 37% (p<0.05) respectively. Dibutyryl.- cAMP but not W-7 also suppressed the secretion of phosphatidylcholine significantly. Dibutyryl-cAMP and W-7 had no significant effect upon [3H] glycerollabeled de novo formed triacylglycerol and phosphatidylcholine, except at the highest concentration tested, 500µM and 50µM respectively, where both triacylglycerol and phosphatidylcholine synthesis were suppressed significantly. Similar findings were obtained on cultured hepatocytes. The molar ratios of newly made triacylglycerol/phosphatidylcholine in the media and cells of hepatocytes were about four times compared to that of McArdle cells, indicating more lipidation and core expansion of nascent lipoprotein particles in hepatocytes. The molar ratio of triacylglycerol/phosphatidylcholinein the medium and cells of cultured McArdle cells was unchanged significantly in the presence of either dibutyryl-cAMP or W-7, However, the molar ratio was decreased 25% (p<0.01) in the presence of dibutyryl-cAMPin the media but not in the cells of cultured hepatocytes.These results suggestthat hepatoma McArdle cell's response to both cAMP-analogue and calmodulin antagonist are comparable to that of normal rat hepatocytes. In addition, the inhibitory effects of dibutyryl-cAMP andW-7 at low concentration are unlikely to be due to the suppression of triacylglycerol and phosphatidylcholine synthesis.