Earlier studies showed that the redundancy of ACG initiation codons enhanced the efficiency of translation initiation by 3-to 6-fold. Evidence presented here shows that this "redundancy effect" can be attributed to a favorable sequence context and, to a lesser extent, remedial initiation. In the case of redundant ACG initiator codons, the second ACG not only acts as a remedial initiation site for scanning ribosomes that skip the first ACG but also enhances the activity of the preceding initiator by providing a preferable "A" at its relative ؉4 position. Hence, nonsuccessive ACG codons can be as effective as successive ACG codons in initiation, if positioned within a similar context. In contrast, redundant GUG initiation codons (GUG/GUG) bear an unfavorable "G" nucleotide at both the ؉4 and ؊3 positions relative to the first and second GUGs, respectively, such that redundant GUG codons act more poorly as translation initiation sites than does a single GUG with a favorable "A" nucleotide in the ؉4 position (ϳ2.5-fold). Thus, the sequence context plays a much more important role than remedial initiation in modulating the efficiency of translational initiation from redundant non-AUG codons.