Abstract: The limits and effect on cell size of silver substitution into synthetic tetrahedrite, Cu10(Zn,Fe,Cd2) Sb4S13, are investigated for comparison with natural tetrahedrite. The limit of Ag substitution into natural zincian tetrahedrite is ∼ 4 atoms per half unit cell and into iron tetrahedrite ∼ 6.5 atoms (with rare exceptions). The cell size of natural tetrahedrite increases with increasing Ag content up to 4 atoms but decreases with further Ag substitution. The highest Ag substitution achieved in synthetic tetrahedrites was 4.7 atoms in Zn2-tetrahedrite, 7.02 atoms in Cd2-tetrahedrite and 6.80 atoms in Fe2-tetrahedrite. The cell size of synthetic tetrahedrites shows a continuous increase with increasing Ag content, the largest cell size of a = 10.927 Å being in the Cd2-tetrahedrite with 7.02 atoms Ag. The iron content of tetrahedrite systematically increased from 1.1 to 2.0 atoms per half unit cell tetrahedrite with increase from 0 to ∼ 4 atoms Ag. The different limit of Ag substitution between Zn2 and Cd2 tetrahedrite can be explained by size constraints on the expanding structure. An explanation is given for a limit of 7 atoms Ag substitution in tetrahedrite using a combined electron band/molecular orbital approach.