(1) The isolated mixtures of ribosomal proteins can be substituted by [14C]-iodoacetamide up to an average of about 2 equivalents per 20,000 dalton. The extent of substitution of single proteins measured after two-dimensional polyacrylamide gel electrophoresis shows that all proteins are reactive. (2) Also in the subunits, all proteins are accessible to substitution. Compared with isolated proteins, however, the reactivity is decreased and the amount of labelling for most proteins ranges as low as 5 to 20%. (3) Reassociation of ribosomal subunits decreases the reactivity of 12 proteins of the small subunit and that of 20 proteins of the large subunit. (4) The presence of messenger inhibits the substitution of 10 proteins of the small subunit and of 6 proteins of the large one. (5) Seven proteins of the small subunit and 3 proteins of the large one are influenced both by the other subunit and by messenger-RNA.