The cyclic nucleotide, guanosine 3',5'-monophosphate (cyclic GMP) appears to serve a critical role in normal cell growth, DNA synthesis, and carcinogenesis (GOLDBERG et al. 1977). Tobacco smoke and hydrazine, a carcinogen which occurs in tobacco and tobacco smoke, have been shown to stimulate guanylate cyclase [E.C. 4.6.1.2], the enzyme that catalyzes the conversion of guanosine triphosphate to guanosine 3',5'-monophosphate (cyclic GMP), (ARNOLD et al. 1977, VESELY and LEVEY 1977a,b). Nicotine, the major alkaloid in tobacco, has been reported to be absorbed by all tissues and sixty-seven percent of nicotine in cigarette-smoke is retained in the lungs of smokers (LARSON et al. 1961). Since nicotine has some tumor promoting activity (BOCK and TSO 1975) we examined the effect of nicotine on guanylate cyclase activity in a variety of tissues.