The mechanism of alkaline ferricyanide oxidation of pyridinium salts has been studied as has the quantitative effect of a 3-substituent upon orientation and reactivity of the nucleus. A3-methyl group activates slightly (_H^MeK= 1·1₃) and directs mainly to C(2); a 3-cyano-group activates appreciably (_H^CNK= 20·2) and also directs mainly to C(2); a 3-methoxycarbonyl group deactivates (_H^CO₂MeK= 0·04₇) and directs exclusively to C(6). The C–H bond cleavage step is not rate-determining in the oxidation of 3-picoline methiodide. Rate-determining addition of OH^– cannot explain the substituent effects. Base-catalysed H–D exchange has been studied; nuclear proton abstraction cannot account for the observed orientation. It is suggested that the rate-determining step is the formation of a complex which reacts with more ferricyanide, oxidation taking place within a second complex. A 3-methyl group facilitates the approach of the polarisable Fe(CN)₆^3–. 3-Substituents exert both electronic and steric effects.