G-protein levels were assessed in liver and brain membranes of lean and obese mice. ADP-ribosylation and immunodetection studies revealed a decrease in the abundance of G8 and G, a-subunits in the liver membranes of obese mice compared with lean mice. In contrast, in brain membranes, the abundance of these proteins was not significantly different between lean and obese mice. Studies at the mRNA level in both liver and brain revealed no difference in gene expression between lean and obese mice. Protein and mRNA studies both showed that G., Gial, Gia2, Goa and G,? subunits are present in brain membranes, and Gia3 is barely detectable. In liver, G,a, Gia2 and G/J subunits are the major constituents, whereas Gial, G1a3 and Goa are barely detectable. It is possible that the differences observed at the protein level are due to different rates of translation of the mRNA. Different rates of release of the a-subunits from the membrane and/or different rates of degradation would also explain these results.