Low temperature electron paramagnetic resonance (EPR) spectroscopy with frequencies between 95 and 345 GHz and magnetic fields up to 12 T have been used to study radicals and metal sites in proteins and small inorganic model complexes. We have studied radicals, Fe, Cu and Mn containing proteins. For S=1/2 systems, the high frequency method can resolve the g-value anisotropy. It was used in mouse ribonucleotide reductase (RNR) to show the presence of a hydrogen bond to the tyrosyl radical oxygen. At 285 GHz the type 2 Cu(II) signal in the complex enzyme laccase is clearly resolved from the Hg(II) containing laccase peroxide adduct. For simple metal sites, the systems over S=1/2 can be described by the spin Hamiltonian: H S =BgS+D[S z 2 -S(S+1)/3+E/D (S x 2 -S y 2 )]. From the high frequency EPR the D-value can be determined directly by, (I) shifts of g e f f for half-integer spin systems with large D-values as observed at 345 GHz on an Fe(II) NO EDTA complex, which is best described as S=3/2 system with D=11.5 cm - 1 , E=0.1 cm - 1 and g x =g y =g z =2.0; (II) measuring the outermost signal, for systems with small D values, distant of (2S-1)*|D| from the center of the spectrum as observed in S=5/2 Fe(III) EDTA. In Mn(II) substituted mouse RNR R2 protein the weakly interacting Mn(II) at X-band could be observed as decoupled Mn(II) at 285 GHz.