The oxidation of isobutane has been found to be catalyzed by 12-molybdophosphates. Among the alkali metals, the substitution of Cs+ for H+ in H3PMo12O40 resulted in the greatest enhancement of the yield of methacrylic acid and the yield reached a maximum around the Cs+ content of 2.5. The rate per specific surface areas of CsxH3-xPMo12O40 (x = 0-3) decreased monotonously with x, It was suggested that isobutane oxidation is a surface-type reaction and the catalytic activity is controlled by the oxidizing ability of the catalyst surface. The catalytic properties of Cs2.5H0.5PMo12O40 were changed by the substitution of metal ions : Ni2+, Mn2+, or Fe3+ substitution greatly increased the sum of yields of methacrylic acid and methacrolein, while the Co2+, Cu2+, Hg2+, Pt2+, or Pd2+ substitution decreased the sum of the yields. Among the transition and precious metals, the highest activity and total yield of methacrylic acid and methacrolein were observed for Ni. The preferred content of Ni was 0.08.