The release of free fatty acids from the epididymal adipose tissue of New Zealand Obese mice, and mice genetically obese because of mutations at the agouti locus, has been studied under various conditions. We found that these fat mice respond normally to cyclic AMP, but are less sensitive to theophylline and least sensitive to epinephrine. In view of these findings and our previous studies of the obese (ob/ob) and diabetic (db/db) mice, it is apparent that in murine obesity, adenyl cyclase is affected more than the lipases. We conclude that the insensitivity to catecholamines is associated with obesity and thus the alleviation of this defect might correct the obesity syndrome. 1 The portion of the work performed by GLW at The Institute for Cancer Research has been supported by U.S.P.H.S. grants CA-06927 and FR-05539 from the National Institutes of Health and by an appropriation from the Commonwealth of Pennsylvania.