The morphology of the Escherichia coli ribosome, i.e., its shape at moderate to low (20–40 Å (1 Å = 0.1 nm)) resolution, provides important constraints in modeling both the folding of ribosomal RNA and the translational process. A new reconstruction, obtained by low-dose cryoelectron microscopy and image processing of single ribosomes, contains clues to the way in which the ribosome interacts with the key functional ligands: the mRNA and the A- and P-site tRNAs. It also suggests possible pathways of the nascent polypeptide chain. From an interpretation of these clues in the light of existing knowledge, a plausible model for the locations and interactions of key components of protein synthesis is suggested.Key words: three-dimensional reconstruction, cryoelectron microscopy, messenger RNA, A- and P-site RNAs, exit tunnels.