1. 1. The mechanism and kinetics of the reactions of cytidine-5′-phosphate with hydroxylamine and O-methylhydroxylamine have been studied. Two types of compounds were formed under the conditions usually employed in biological studies with nucleic acids. The first product arises by two consecutive reactions: reversible addition of the reagent to the C5-C6double bond of the cytosine nucleus and subsequent irreversible substitution of the amino group by a second molecule of the reagent. The second product is formed by direct substitution of the amino group. 2. 2. The reaction of the protonated cytosine nucleus and an uncharged molecule of the reagent is about 10 times faster than the reaction of the uncharged cytosine nucleus with uncharged reagent. 3. 3. The rates of the further conversions of major products have been measured under a wide variety of conditions. 4. 4. The ratio of reaction products strongly depends on the reaction conditions because of the reversibility of the addition to C5-C6double bond. Particularly, an increase of pH and reagent concentration results in the prevalence of the first type of products. 5. 5. The rates of reactions and the ratio of reaction products strongly depend on substitution at the cytosine nucleus. N3-methylation of the cytosine residue leads to acceleration of both of the reactions. Methylation of the amino group decreases the rate of C5-C6addition but reduces much stronger the rate of direct substitution at C4. 6. 6. The data obtained comprehensively characterise the reactivity of the cytosine nucleus towards hydroxylamine and O-methylhydroxylamine and the chemical properties of the products of modification providing a firm basis for the interpretation of the results of functional studies made with polynucleotides and nucleoproteins. © 1971.