Statistical analysis of lipoprotein and non-lipoprotein signal peptides reveals that the two classes differ significantly only in the region close to the signal peptidase cleavage site. This region is apolar and has the consensus sequence LA(G,A) decreases C in the lipoproteins, but is polar and has small, uncharged residues in positions -3 and -1 in the non-lipoproteins. A simple search for matches to the lipoprotein consensus cleavage site suffices to discriminate between the two groups with close to 100% reliability.