Glucagon1–6 has a maximum lipolytic activity (Lmax) in the rat adipocyte which is 66% of that of glucagon. The N∊-guanidyl derivative, modified at Lys12, has about the same Lmax as glucagon1–6. Modifying the carboxyl groups of glucagon with glycinamide or removing the COON-terminal residues with cyanogen bromide reduces Lmax to less than 25% of the level of glucagon. The potency of each of these analogs (A50) in μM is as follows: glucagon 6 × 10−3; glucagon1–6 2 × 10−2; N∊-guanidyl glucagon 9 × 10−3; glycinamide glucagon 10−2; cyanogen bromide peptide of glucagon 2 × 10−1. The ability of all of the glucagon analogs to stimulate adenyl cyclase was somewhat less than their tipolytic activities with the exception of the glycin-amide derivative and the cyanogen bromide peptide, which were slightly more active in stimulating adenyl cyclase than in lipolysis. Glucagon1–6 is much more potent in stimulating adipocyte than liver adenyl cyclase.