The influence of changing concentrations of GDP, methionyl-tRNAi, eIF-2 and eIF-2B on possible rates of initiation of protein synthesis have been explored in calculations based on previously derived rate constants for interaction of the components involved in formation of ternary or quaternary complexes of eIF-2B, eIF-2, GTP and Met-tRNAi. When allowance is made for the limitation of diffusional coefficients imposed on macromolecules by the intracellular milieu it is apparent that recent estimates by Rowlands et al. (Eur. J. Biochem. 175, 93:1988) of higher concentrations of eIF-2 and eIF-2B in cells than hitherto proposed become necessary to support known rates of initiation. Under these conditions changing concentrations of met-tRNAi as proposed by Cooper and Braverman (J. Biol. Chem. 256, 7461:1981) are likely to have an important regulating influence.