Previous studies have reported that the 3' half of the small, S, RNA species of the WE strain of lymphocytic choriomeningitis (LCM) virus codes for the viral nucleoprotein in a subgenomic, viral-complementary, mRNA species (Romanowski, V. and Bishop, D.H.L. (1985) Virus Res. 2, 35-51). The complete sequence of the LCM-WE S RNA has now been obtained, indicating that the 5' half of the RNA codes for the viral glycoprotein precursor in a viral-sense sequence that does not overlap the N gene. It is concluded that, like Pichinde virus (Auperin, D. et al. (1984) J. Virol. 52, 897-904), LCM has an ambisense S RNA coding strategy. The LCM-WE S RNA is 3375 nucleotides in length, has a size of 1.14 X 10(6) Da and base composition of 26.1% A, 23.2% C, 21.5% G, 29.2% U. The 3' and 5' end sequences of the S RNA are complementary for some 30 nucleotides, depending on the arrangement. The non-coding regions at the two ends are 77 (5') and 60 (3') nucleotides long. The glycoprotein precursor has a primary amino acid size of 56293 Da and is rich in potential glycosylation sites as well as histidine and cysteine residues. It has both amino and carboxy proximal hydrophobic regions. The LCM-WE S RNA and predicted protein sequence data have been compared to those of Pichinde arena-virus. Extensive RNA and protein sequence homology exists for the two S RNA species, although the homology for the glycoprotein sequences of the two viruses (39%) is less than the 50% observed for the two viral nucleoproteins.