Geodia baretti (Bowerbank) Lamarck is predominant on the deep bottoms in the Koster fjord on the northern Swedish west coast. The sponge referred to as Geodia gigas by Ackermann and List (4,5) must be G. baretti, and Geodia rynodium of DeRosa et al. (10) is actually Geodia rydonium (personal communication, Dr. O.S. Tendal, Zoological Museum, University of Copenhagen). Chemical investigations of the genus Geodia (phylum Porifera, order Tetraactinellidae, class Demospongiae, family Geodidae) are very limited. In a screening of crude extracts of marine organisms, aqueous and MeOH extracts of G. baretti exhibited strong contractile activity in the isolated guinea-pig ileum assay, and the aqueous extract was devoid of lectinlike activity. The EtOH extracts of freshly collected material, on LH-20 column chromatography, gave rise to seven fractions all exhibiting either contractile activity or inhibition of electrically stimulated guinea-pig ileum. Only fractions 5 and 6 were further investigated and resulted in the identification of barettin, adenosine (fraction 6), histamine (responsible for the main activity of the crude extract), and inosine (fraction 5), identified by comparison with authentic samples. Fraction 5, in addition, yielded three N-methylated nucleosides, namely 3-methylcytidine (3mCyd), 3-methyl-2'-deoxycytidine (3mdCyd), and 3-methyl-2'-deoxyuridine (3mdUrd). The structures of the three nucleosides were inferred from comparison of fabms, 1H-nmr, and 13C-nmr data with values reported for the synthetic compounds. The presence of 3mdUrd is curious, because deoxyuridine is not naturally occurring, and this compound could be formed by mild hydrolysis of 3mdCyd during the isolation procedure. Although methylation of polynucleotide and oligonucleotide sequences is a well known phenomenon, methylation of DNA-bound deoxycytosine is only known to occur in position 5. 3mCyd has been isolated from yeast RNA hydrolysates and human urine. We believe that the present conditions of extraction and isolation are far too mild to produce nucleosides by hydrolysis of polymeric material. Hence, at least 3mCyd and 3mdCyd and possibly also 3mdUrd are natural products present as the free nucleosides. To the best of our knowledge, 3mdCyd and 3mdUrd have never been found as free natural products before. The biological activities of the isolated compounds showed that only 3mCyd and 3mdCyd exhibit strong contractile activity in the ileum assay, whereas most other nucleosides have either no effect or inhibitory effect on the electrically stimulated preparation. The products described here are present only in minute amounts (based on wet wt: inosine 4×10^-3%, 3mdCyd 6×10^-3%, 3mdUrd 6×10^-4%, histamine 2×10^-3%, barettin 1×10^-3%, adenosine 3×10^-3%). It is an open question whether these products originate with the sponge or with some associated microorganisms.