The effect of cupric ions on the initiation protein synthesis rate of the human endometrium was studied. Addition of copper to the complete ribosomal system decreased the binding of [ 3H]Met-tRNA(i) to the isolated ribosomes with a plateau at about 70% inhibition with concentrations higher than 150 μM. The initiation activity was GTP-dependent with a maximum at 2 mM. This activity was very rapid, requiring 5 min to complete the reaction. Incubation of isolated initiation factors with copper (300 μM) inhibited the formation of the ternary complex. When the complete system was reconstituted with salt-washed ribosomes after ternary complex formation, no significant change on the inhibition pattern was observed. Addition of initiation factors to 5-min preincubated salt-washed ribosomes with 300 μM copper, after the elimination of excess copper, induced only a 12% decrease on Met-tRNA(i) binding. This effect was not modified by the presence of Sparsomycin, an elongation inhibitor. It was concluded that copper interferes with the initiation process, probably at the ternary complex formation level.