P37 (F13L gene product), the most abundant protein in the envelope of the extracellular virus form of the prototype poxvirus, vaccinia virus (VV), is a crucial player in the process leading to acquisition of the envelope, virus egress and transmission, We have cloned and sequenced a swinepox virus (SPV) gene homologous to W p13L. The SPV gene product, termed P42, was 54% identical to P37, the W F13L gene product, and, among the poxviruses, was most similar (73% identity) to the myxoma virus homologue, The SPV P42 gene contained late transcription signals and was expressed only at late times during infection, The protein was palmitylated, and showed an intracellular distribution similar to that of W P37, both by immunofluorescence and by subcellular fractionation, As with W P37, SPV P42 was incorporated in extracellular enveloped SPV particles, but was absent from the intracellular mature virus form, To check the ability of SPV P42 to function in the context of W infection, we inserted the SPV gene into a W deficient in P37, which is severely blocked in virus envelopment and cell-to-cell transmission, Despite correct expression of SPV P42, the resulting recombinant W showed no rescue of extracellular virus formation or cell-to-cell virus spread, The lack of function of SPV P42 in the W genetic background suggests that specific interactions between SPV P42 or W P37 and other viral proteins is required to drive the envelopment process.